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Progress and Principle of Drug Nanocrystals for Tumor Targeted Delivery

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Abstract

Drugs are referred to as drug nanocrystals when they exist as nanoscale crystal structures. This kind of nanocarrier has been widely utilized to increase the solubility and absorption for poorly aqueous soluble drugs after oral administration, or prolong the drug circulation when intravenous administration. The systemic cytotoxicity caused by antitumor drugs usually come from the nonspecific drug distribution. To solve the disadvantage of poor targetability, drug nanocrystals for tumor targeted delivery have been developed in recent years. In this review, the targeting mechanisms of various surface modified drug nanocrystals are introduced with the focus on passive targeting, active targeting and stimuli-responsive targeting in details. Function and application of common surface modified materials are also discussed.

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Abbreviations

Topo I:

topoisomerase I

PEG:

polyethylene glycol

PCL:

polycaprolactone

mPEG:

Polyethylene glycol monomethyl ether

HA:

hyaluronic acid

CLT-NCs:

cilostazol nanocrystals

DW:

distilled water

CSOA-DOX NCs:

doxorubicin nanocrystals modified with chondroitin sulfate

DOX/PEG-PCL:

doxorubicin loaded micelles modified with polycaprolactone and polyethylene glycol

PTX-NCs-Gel:

paclitaxel nanocrystals-hydrogel system

EPR:

high permeability and retention

IDM/PTX NCs:

indomethacin modified paclitaxel nanocrystals

MTO NCs:

mitoxantrone nanocrystals

RGD:

Arginine-Glycine-Aspartic acid

CS:

chondroitin sulfate

HAase:

hyaluronidase

FA:

Folic acid

HCPT:

hydroxycamptothecin

HCPT NCs@AuNPs-Zein-PFA:

Au nanoparticles as the core and FA-conjugated amphiphilic Zein-PFA as the shell with encapsulation of HCPT nanocrystals

PTX NCs@PDA-PEG-RGD:

paclitaxel nanocrystals with PEG and RGD peptide

Tf R:

transferrin receptors

DTX:

docetaxel

Tf-PTX-NCs:

transferrin-modified paclitaxel nanocrystals

CNS:

central nervous system

EGFR:

epidermal growth factor receptor

PTX@PCL-PEG-Herceptin:

Herceptin-conjugated, paclitaxel loaded PCL-PEG worm-like nanocrystals

ZnS:Mn NCs:

Mn-doped zinc sulphide nanocrystals

DAI:

the disease activity index

MMPs:

matrix metalloproteinases

COX-2:

cyclooxygenase-2

PKD1:

protein kinase D1

MNCs:

magnetic nanocrystals

ACMF:

alternating current magnetic field

ROS:

reactive oxygen species

GSH:

glutathione

OA:

oleic acid

NIR:

near-infrared

PTT:

photothermal therapy

PDT:

photodynamic therapy

LCST:

low critical solution temperature

PVA:

polyvinyl alcohol

CAP1AG4CH5@CUNCs:

chitosan (CH)/alginate (AG)/cellulose acetate phthalate (CAP)multi-layer curcumin nanocrystals

CNC-SS-PD3/pCMV-CD/5-FC:

cytosine deaminase/5-fluorocytosine loaded on cellulose nanocrystals (CNCs) made from natural cotton with poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) linked by disulfide bonds

CeVO4/Au NCs:

semiconductor nanomaterials through loading plasmonic metal nanoparticle

TMZ-Bi2O3@PVA:

Bi2O3 nanocrystals fixed in polyvinyl alcohol (PVA) nanogels with temozolomide

RGD-RBC-DTX NCs:

c(RGDyK) peptide modified and red blood cell membrane encapsulated docetaxel nanocrystals.

References

  1. Malamatari M, Taylor KMG, Malamataris S, Douroumis D, Kachrimanis K. Pharmaceutical nanocrystals: production by wet milling and applications. Drug Discov Today. 2018;23(3):534–47. https://doi.org/10.1016/j.drudis.2018.01.016.

    Article  CAS  PubMed  Google Scholar 

  2. Liang Y, Fu X, Du C, Xia H, Lai Y, Sun Y. Enzyme/pH-triggered anticancer drug delivery of chondroitin sulfate modified doxorubicin nanocrystal. Artif Cell Nanomed Biotechnol. 2020;48(1):1114–24. https://doi.org/10.1080/21691401.2020.1813741.

    Article  CAS  Google Scholar 

  3. Mao Y, Liu J, Shi T, Chen G, Wang S. A Novel Self-Assembly Nanocrystal as Lymph Node-Targeting Delivery System: Higher Activity of Lymph Node Targeting and Longer Efficacy Against Lymphatic Metastasis. AAPS PharmSciTech. 2019;20(7):292. https://doi.org/10.1208/s12249-019-1447-3.

    Article  CAS  PubMed  Google Scholar 

  4. Zhang HW, Dang Q, Zhang ZW, Wu FS. Development, characterization and evaluation of doxorubicin nanostructured lipid carriers for prostate cancer. J BUON. 2017;22(1):102–11.

    PubMed  Google Scholar 

  5. Kim HM, Lee GH, Kuh HJ, Kwak BK, Lee J. Liposomal doxorubicin-loaded chitosan microspheres capable of controlling release of doxorubicin for anti-cancer chemoembolization: in vitro characteristics. J Drug Deliv Sci Technol. 2013;23(3):283–6.

    Article  CAS  Google Scholar 

  6. Wang J, Muhammad N, Li T, Wang H, Liu Y, Liu B, Zhan H. Hyaluronic Acid-Coated Camptothecin Nanocrystals for Targeted Drug Delivery to Enhance Anticancer Efficacy. Mol Pharm. 2020;17(7):2411–25. https://doi.org/10.1021/acs.molpharmaceut.0c00161.

    Article  CAS  PubMed  Google Scholar 

  7. Gan MY, Zhang WP, Wei SJ, Dang HW. The influence of mPEG-PCL and mPEG-PLGA on encapsulation efficiency and drug-loading of SN-38 NPs. Artif Cell Nanomed Biotechnol. 2017;45(2):389–97. https://doi.org/10.3109/21691401.2016.1167700.

    Article  CAS  Google Scholar 

  8. Hou Z, Zhou S, Cui F, Hang Y, Yi Y. Preparation and characterization of hydroxycamptothecin-loaded Poly(D,L-lactic acid) nanoparticles with high drug loading capacity. In: Zhang H, Jin D, editors. Advanced Research on Material Engineering, Chemistry, Bioinformatics Ii2012. p. 503.

  9. Lin YA, Cheetham AG, Zhang PC, Ou YC, Li YG, Liu GS, Hermida-Merino D, Hamley IW, Cui H. Multiwalled Nanotubes Formed by Catanionic Mixtures of Drug Amphiphiles. Acs Nano. 2014;8(12):12690–700. https://doi.org/10.1021/nn505688b.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Fang S, Hou YP, Ling LB, Wang DQ, Ismail M, Du YW, et al. Dimeric camptothecin derived phospholipid assembled liposomes with high drug loading for cancer therapy. Colloids Surf B. 2018;166:235–44. https://doi.org/10.1016/j.colsurfb.2018.02.046.

    Article  CAS  Google Scholar 

  11. Sharma S, Verma A, Pandey G, Mittapelly N, Mishra PR. Investigating the role of Pluronic-g-Cationic polyelectrolyte as functional stabilizer for nanocrystals: Impact on Paclitaxel oral bioavailability and tumor growth. Acta Biomater. 2015;26:169–83. https://doi.org/10.1016/j.actbio.2015.08.005.

    Article  CAS  PubMed  Google Scholar 

  12. Liu Y, Huang L, Liu F. Paclitaxel Nanocrystals for Overcoming Multidrug Resistance in Cancer. Mol Pharm. 2010;7(3):863–9. https://doi.org/10.1021/mp100012s.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lv PP, Wei W, Yue H, Yang TY, Wang LY, Ma GH. Porous Quaternized Chitosan Nanoparticles Containing Paclitaxel Nanocrystals Improved Therapeutic Efficacy in Non-Small-Cell Lung Cancer after Oral Administration. Biomacromolecules. 2011;12(12):4230–9. https://doi.org/10.1021/bm2010774.

    Article  CAS  PubMed  Google Scholar 

  14. Filippousi M, Papadimitriou SA, Bikiaris DN, Pavlidou E, Angelakeris M, Zamboulis D, Tian H, van Tendeloo G. Novel core-shell magnetic nanoparticles for Taxol encapsulation in biodegradable and biocompatible block copolymers: Preparation, characterization and release properties. Int J Pharm. 2013;448(1):221–30. https://doi.org/10.1016/j.ijpharm.2013.03.025.

    Article  CAS  PubMed  Google Scholar 

  15. Liang N, Sun SP, Hong J, Tian JZ, Fang L, Cui FD. In vivo pharmacokinetics, biodistribution and antitumor effect of paclitaxel-loaded micelles based on alpha-tocopherol succinate-modified chitosan. Drug Deliv. 2016;23(8):2651–60. https://doi.org/10.3109/10717544.2015.1045103.

    Article  CAS  PubMed  Google Scholar 

  16. Choi JS. Design of Cilostazol Nanocrystals for Improved Solubility. J Pharm Innov. 2019;15(3):416–23. https://doi.org/10.1007/s12247-019-09391-7.

    Article  Google Scholar 

  17. Zhang X, Li L, Gao X, Zhang H, Gao J, Du YM, et al. In Vitro Evaluation of Quercetin Nanocrystals with Different Particle Sizes. J Nanosci Nanotechnol. 2020;20(10):6469–74. https://doi.org/10.1166/jnn.2020.18580.

    Article  CAS  PubMed  Google Scholar 

  18. Kakran M, Shegokar R, Sahoo NG, Al Shaal L, Li L, Mueller RH. Fabrication of quercetin nanocrystals: Comparison of different methods. Eur J Pharm Biopharm. 2012;80(1):113–21. https://doi.org/10.1016/j.ejpb.2011.08.006.

    Article  CAS  PubMed  Google Scholar 

  19. He X, Song H. Study on preparation and characteristics of naringenin nanocrystals in vitro. Chin J Hosp Pharm. 2016;36(4):289–93.

    Google Scholar 

  20. Ige PP, Baria RK, Gattani SG. Fabrication of fenofibrate nanocrystals by probe sonication method for enhancement of dissolution rate and oral bioavailability. Colloids Surf B. 2013;108:366–73. https://doi.org/10.1016/j.colsurfb.2013.02.043.

    Article  CAS  Google Scholar 

  21. Desai SK, Mondal D, Bera S. First-line anti-tubercutilosis drugs-loaded starch nanocrystals for combating the threat of M. tuberculosis H37Rv strain. Carbohydr Res. 2020;495:108070. https://doi.org/10.1016/j.carres.2020.108070.

    Article  CAS  PubMed  Google Scholar 

  22. George M, Ghosh I. Identifying the correlation between drug/stabilizer properties and critical quality attributes (CQAs) of nanosuspension formulation prepared by wet media milling technology. Eur J Pharm Sci. 2013;48(1-2):142–52. https://doi.org/10.1016/j.ejps.2012.10.004.

    Article  CAS  PubMed  Google Scholar 

  23. Yue P, Li Y, Wan J, Yang M, Zhu W, Wang C. Study on formability of solid nanosuspensions during nanodispersion and solidification: I. Novel role of stabilizer/drug property. Int J Pharm. 2013;454(1):269–77. https://doi.org/10.1016/j.ijpharm.2013.06.050.

    Article  CAS  PubMed  Google Scholar 

  24. Singhal D, Curatolo W. Drug polymorphism and dosage form design: a practical perspective. Adv Drug Del Rev. 2004;56(3):335–47. https://doi.org/10.1016/j.addr.2003.10.008.

    Article  CAS  Google Scholar 

  25. Lai F, Sinico C, Ennas G, Marongiu F, Marongiu G, Fadda AM. Diclofenac nanosuspensions: Influence of preparation procedure and crystal form on drug dissolution behaviour. Int J Pharm. 2009;373(1-2):124–32. https://doi.org/10.1016/j.ijpharm.2009.01.024.

    Article  CAS  PubMed  Google Scholar 

  26. Lestari MLAD, Mueller RH, Moeschwitzer JP. Systematic Screening of Different Surface Modifiers for the Production of Physically Stable Nanosuspensions. J Pharm Sci. 2015;104(3):1128–40. https://doi.org/10.1002/jps.24266.

    Article  CAS  PubMed  Google Scholar 

  27. Van Eerdenbrugh B, Vermant J, Martens JA, Froyen L, Van Humbeeck J, Augustijns P, et al. A Screening Study of Surface Stabilization during the Production of Drug Nanocrystals. J Pharm Sci. 2009;98(6):2091–103. https://doi.org/10.1002/jps.21563.

    Article  CAS  PubMed  Google Scholar 

  28. Lee J, Choi JY, Park CH. Characteristics of polymers enabling nano-comminution of water-insoluble drugs. Int J Pharm. 2008;355(1-2):328–36. https://doi.org/10.1016/j.ijpharm.2007.12.032.

    Article  CAS  PubMed  Google Scholar 

  29. Zhang W, Yu L, Ji T, Wang C. Tumor Microenvironment–responsivepeptide-based supramolecular drug delivery system. Front Chem. 2020;8. https://doi.org/10.3389/fchem.2020.00549.

  30. Duan X, Li Y. Physicochemical Characteristics of Nanoparticles Affect Circulation, Biodistribution, Cellular Internalization, and Trafficking. Small. 2013;9(9-10):1521–32. https://doi.org/10.1002/smll.201201390.

    Article  CAS  PubMed  Google Scholar 

  31. Hollis CP, Weiss HL, Leggas M, Evers BM, Gemeinhart RA, Li T. Biodistribution and bioimaging studies of hybrid paclitaxel nanocrystals: lessons learned of the EPR effect and image-guided drug delivery. J Control Release. 2013;172(1):12–21. https://doi.org/10.1016/j.jconrel.2013.06.039.

    Article  CAS  PubMed  Google Scholar 

  32. Yuan F, Dellian M, Fukumura D, Leunig M, Berk DA, Torchilin VP, Jain RK. Vascular permeability in a human tumor xenograft: molecular size dependence and cutoff size. Cancer Res. 1995;55(17):3752–6.

    CAS  PubMed  Google Scholar 

  33. Zhang C, Long L, Xiong Y, Wang C, Peng C, Yuan Y, Liu Z, Lin Y, Jia Y, Zhou X, Li X. Facile Engineering of Indomethacin-Induced Paclitaxel Nanocrystal Aggregates as Carrier-Free Nanomedicine with Improved Synergetic Antitumor Activity. ACS Appl Mater Interfaces. 2019;11(10):9872–83. https://doi.org/10.1021/acsami.8b22336.

    Article  CAS  PubMed  Google Scholar 

  34. Mei X, Li M, Gao G, Ma S, Liu C, Hu X. Initial analysis of nano carrier targeted drug delivery system: misunderstanding, barriers and strategy. Scientia Sinica Vitae. 2016;46(11):1249–58.

    Article  Google Scholar 

  35. Angelopoulou A, Kolokithas Ntoukas A, Fytas C, Avgoustakis K. Folic acid-functionalized, condensed magnetic nanoparticles for targeted delivery of doxorubicin to tumor cancer cells overexpressing the folate receptor. ACS Omega. 2019;4(26):22214–27. https://doi.org/10.1021/acsomega.9b03594.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Wang H, Zhu W, Huang Y, Li Z, Jiang Y, Xie Q. Facile encapsulation of hydroxycamptothecin nanocrystals into zein-based nanocomplexes for active targeting in drug delivery and cell imaging. Acta Biomater. 2017;61:88–100. https://doi.org/10.1016/j.actbio.2017.04.017.

    Article  CAS  PubMed  Google Scholar 

  37. Huang ZG, Lv FM, Wang J, Cao SJ, Liu ZP, Liu Y, Lu WY. RGD-modified PEGylated paclitaxel nanocrystals with enhanced stability and tumor-targeting capability. Int J Pharm. 2019;556:217–25. https://doi.org/10.1016/j.ijpharm.2018.12.023.

    Article  CAS  PubMed  Google Scholar 

  38. Xie J, Yan C, Yan Y, Chen L, Song L, Zang F, An Y, Teng G, Gu N, Zhang Y. Multi-modal Mn-Zn ferrite nanocrystals for magnetically-induced cancer targeted hyperthermia: a comparison of passive and active targeting effects. Nanoscale. 2016;8(38):16902–15. https://doi.org/10.1039/c6nr03916b.

    Article  CAS  PubMed  Google Scholar 

  39. Khoo TC, Tubbesing K, Rudkouskaya A, Rajoria S, Sharikova A, Barroso M, et al. Quantitative label-free imaging of iron-bound transferrin in breast cancer cells and tumors. Redox Biol. 2020;36:101617. https://doi.org/10.1016/j.redox.2020.101617.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Lu Y, Wang Z, Li T, McNally H, Park K, Sturek M. Development and evaluation of transferrin-stabilized paclitaxel nanocrystal formulation. J Control Release. 2014;176:76–85. https://doi.org/10.1016/j.jconrel.2013.12.018.

    Article  CAS  PubMed  Google Scholar 

  41. Choi JS, Park JS. Development of docetaxel nanocrystals surface modified with transferrin for tumor targeting. Drug Des Devel Ther. 2016;11:17–26. https://doi.org/10.2147/dddt.s122984.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Qi Y, Zhang T, Jing C, Liu S, Zhang C, Alvarez PJJ, Chen W. Nanocrystal facet modulation to enhance transferrin binding and cellular delivery. Nat Commun. 2020;11(1):1262. https://doi.org/10.1038/s41467-020-14972-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Sun W, Du Y, Liang X, Yu C, Fang J, Lu W, et al. Synergistic triple-combination therapy with hyaluronic acid-shelledPPy/CPT nanoparticles results in tumor regression and prevents tumor recurrence and metastasis in 4T1 breast cancer. Biomater. 2019;217:119264. https://doi.org/10.1016/j.biomaterials.2019.119264.

    Article  CAS  Google Scholar 

  44. Chen ZJ, He N, Chen MH, Zhao L, Li XH. Tunable conjugation densities of camptothecin on hyaluronic acid for tumor targeting and reduction-triggered release. Acta Biomate. 2016;43:195–207. https://doi.org/10.1016/j.actbio.2016.07.020.

    Article  CAS  Google Scholar 

  45. Liu P, Chen N, Yan L, Gao F, Ji D, Zhang S, Zhang L, Li Y, Xiao Y. Preparation, characterisation and in vitro and in vivo evaluation of CD44-targeted chondroitin sulphate-conjugated doxorubicin PLGA nanoparticles. Carbohydr Polym. 2019;213:17–26. https://doi.org/10.1016/j.carbpol.2019.02.084.

    Article  CAS  PubMed  Google Scholar 

  46. Zhang BZ, Cheng GG, Zheng MB, Han JY, Wang BB, Li MX, Chen J, Xiao T, Zhang J, Cai L, Li S, Fan X. Targeted delivery of doxorubicin by CSA-binding nanoparticles for choriocarcinoma treatment. Drug Deliv. 2018;25(1):461–71. https://doi.org/10.1080/10717544.2018.1435750.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Ma MF, Shang WQ, Jia RX, Chen RJ, Zhao M, Wang CQ, Tian M, Yang S, Hao A. A novel folic acid hydrogel loading beta-cyclodextrin/camptothecin inclusion complex with effective antitumor activity. J Incl Phenom Macrocycl Chem. 2020;96(1-2):169–79. https://doi.org/10.1007/s10847-019-00962-2.

    Article  CAS  Google Scholar 

  48. Mansur AAP, Amaral-Junior JC, Carvalho SM, Carvalho IC, Mansur HS. Cu-In-S/ZnS@carboxymethylcellulose supramolecular structures: Fluorescent nanoarchitectures for targeted-theranostics of cancer cells. Carbohydr Polym. 2020;247:116703. https://doi.org/10.1016/j.carbpol.2020.116703.

    Article  CAS  PubMed  Google Scholar 

  49. Hao HQ, Ma QM, He F, Yao P. Doxorubicin and Fe3O4 loaded albumin nanoparticles with folic acid modified dextran surface for tumor diagnosis and therapy. J Mater Chem B. 2014;2(45):7978–87. https://doi.org/10.1039/c4tb01359j.

    Article  CAS  PubMed  Google Scholar 

  50. Yan Y, Wang RZ, Hu Y, Sun RY, Song T, Shi XY, Yin S. Stacking of doxorubicin on folic acid-targeted multiwalled carbon nanotubes for in vivo chemotherapy of tumors. Drug Deliv. 2018;25(1):1607–16. https://doi.org/10.1080/10717544.2018.1501120.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Liang XH, Fan J, Zhao YY, Cheng M, Wang XJ, Jin RY, Sun T. A targeted drug delivery system based on folic acid-functionalized upconversion luminescent nanoparticles. J Biomater Appl. 2017;31(9):1247–56. https://doi.org/10.1177/0885328217701289.

    Article  CAS  PubMed  Google Scholar 

  52. Peng J, Chen J, Xie F, Bao W, Xu H, Wang H, Xu Y, du Z. Herceptin-conjugated paclitaxel loaded PCL-PEG worm-like nanocrystal micelles for the combinatorial treatment of HER2-positive breast cancer. Biomater. 2019;222:119420. https://doi.org/10.1016/j.biomaterials.2019.119420.

    Article  CAS  Google Scholar 

  53. Büyükköroğlu G, Şenel B, Gezgin S, Dinh T. The simultaneous delivery of paclitaxel and Herceptin® using solid lipid nanoparticles: In vitro evaluation. J Drug Deliv Sci Technol. 2016;35:98–105. https://doi.org/10.1016/j.jddst.2016.06.010.

    Article  CAS  Google Scholar 

  54. Shi J, Liu S, Yu Y, He C, Tan L, Shen Y-M. RGD peptide-decorated micelles assembled from polymer–paclitaxel conjugates towards gastric cancer therapy. Colloids Surf B. 2019;180:58–67. https://doi.org/10.1016/j.colsurfb.2019.04.042.

    Article  CAS  Google Scholar 

  55. Zhu R, Tian Y. Preparation and evaluation of RGD and TAT co-modified docetaxel-loaded liposome. Drug Des, Dev Ther. 2017;11:3481–9. https://doi.org/10.2147/dddt.S149620.

    Article  CAS  Google Scholar 

  56. Wang L, Zhang T, Huo M, Guo J, Chen Y, Xu H. Construction of Nucleus-Targeting Iridium Nanocrystals for Photonic Hyperthermia-Synergized Cancer Radiotherapy. Small. 2019;15(47):1903254. https://doi.org/10.1002/smll.201903254.

    Article  CAS  Google Scholar 

  57. Liu W, Lin Q, Fu Y, Huang S, Guo C, Li L, Wang L, Zhang Z, Zhang L. Target delivering paclitaxel by ferritin heavy chain nanocages for glioma treatment. J Control Release. 2020;323:191–202. https://doi.org/10.1016/j.jconrel.2019.12.010.

    Article  CAS  PubMed  Google Scholar 

  58. Mei D, Gong L, Zou Y, Yang D, Liu H, Liang Y, Sun N, Zhao L, Zhang Q, Lin Z. Platelet membrane-cloaked paclitaxel-nanocrystals augment postoperative chemotherapeutical efficacy. J Control Release. 2020;324:341–53. https://doi.org/10.1016/j.jconrel.2020.05.016.

    Article  CAS  PubMed  Google Scholar 

  59. Bang KH, Na YG, Huh HW, Hwang SJ, Kim MS, Kim M, et al. The Delivery Strategy of Paclitaxel Nanostructured Lipid Carrier Coated with Platelet Membrane. Cancers (Basel). 2019;11(6). https://doi.org/10.3390/cancers11060807.

  60. Chai Z, Ran D, Lu L, Zhan C, Ruan H, Hu X, Xie C, Jiang K, Li J, Zhou J, Wang J, Zhang Y, Fang RH, Zhang L, Lu W. Ligand-Modified cell membrane enables the targeted delivery of drug nanocrystals to glioma. ACS Nano. 2019;13(5):5591–601. https://doi.org/10.1021/acsnano.9b00661.

    Article  CAS  PubMed  Google Scholar 

  61. Jiang X, Wang KK, Zhou ZG, Zhang YF, Sha HZ, Xu QP, Wu J, Wang J, Wu J, Hu Y, Liu B. Erythrocyte membrane nanoparticles improve the intestinal absorption of paclitaxel. Biochem Biophys Res Commun. 2017;488(2):322–8. https://doi.org/10.1016/j.bbrc.2017.05.042.

    Article  CAS  PubMed  Google Scholar 

  62. Chen H, Sha HZ, Zhang LR, Qian HQ, Chen FJ, Ding NQ, Ji L, Zhu A, Xu Q, Meng F, Yu L, Zhou Y, Liu B. Lipid insertion enables targeted functionalization of paclitaxel-loaded erythrocyte membrane nanosystem by tumor-penetrating bispecific recombinant protein. Int J Nanomed. 2018;13:5347–59. https://doi.org/10.2147/ijn.S165109.

    Article  CAS  Google Scholar 

  63. Wang S, Low PS. Folate-mediated targeting of antineoplastic drags, imaging agents, and nucleic acids to cancer cells. J Control Release. 1998;53(1-3):39–48. https://doi.org/10.1016/s0168-3659(97)00236-8.

    Article  CAS  PubMed  Google Scholar 

  64. Parker N, Turk MJ, Westrick E, Lewis JD, Low PS, Leamon CP. Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay. Anal Biochem. 2005;338(2):284–93. https://doi.org/10.1016/j.ab.2004.12.026.

    Article  CAS  PubMed  Google Scholar 

  65. Chen X, Zhu Q, Xu X, Shen S, Zhang Y, Mo R. Sequentially site-specific delivery of apoptotic protein and tumor-suppressor gene for combination cancer therapy. Small. 2019;15(40). https://doi.org/10.1002/smll.201902998.

  66. Zhang X, Liang N, Gong X, Kawashima Y, Cui F, Sun S. Tumor-targeting micelles based on folic acid and alpha-tocopherol succinate conjugated hyaluronic acid for paclitaxel delivery. Colloids Surf B. 2019;177:11–8. https://doi.org/10.1016/j.colsurfb.2019.01.044.

    Article  CAS  Google Scholar 

  67. Narmani A, Mohammadnejad J, Yavari K. Synthesis and evaluation of polyethylene glycol- and folic acid-conjugated polyamidoamine G4 dendrimer as nanocarrier. J Drug Deliv Sci Technol. 2019;50:278–86. https://doi.org/10.1016/j.jddst.2019.01.037.

    Article  CAS  Google Scholar 

  68. Qin YT, Peng H, He XW, Li WY, Zhang YK. pH-Responsive Polymer-Stabilized ZIF-8 Nanocomposites for Fluorescence and Magnetic Resonance Dual-Modal Imaging-Guided Chemo-/Photodynamic Combinational Cancer Therapy. ACS Appl Mater Interfaces. 2019;11(37):34268–81. https://doi.org/10.1021/acsami.9b12641.

    Article  CAS  PubMed  Google Scholar 

  69. Pan L, Zhao Y, Yuan Z, Qin G. Research advances on structure and biological functions of integrins. Springerplus. 2016;5:1094. https://doi.org/10.1186/s40064-016-2502-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Cheng Y, Ji YH. RGD-modified polymer and liposome nanovehicles: Recent research progress for drug delivery in cancer therapeutics. Eur J Pharm Sci. 2019;128:8–17. https://doi.org/10.1016/j.ejps.2018.11.023.

    Article  CAS  PubMed  Google Scholar 

  71. Daniels TR, Delgado T, Helguera G, Penichet ML. The transferrin receptor part II: Targeted delivery of therapeutic agents into cancer cells. Clin Immunol. 2006;121(2):159–76. https://doi.org/10.1016/j.clim.2006.06.006.

    Article  CAS  PubMed  Google Scholar 

  72. Li HY, Qian ZM. Transferrin/transferrinreceptor-mediated drug delivery. Med Res Rev. 2002;22(3):225–50. https://doi.org/10.1002/med.10008.

  73. Ji B, Maeda A, Higuchi M, Inoue K, Akita H, Harashima H, et al. Pharmacokinetics and brain uptake of lactoferrin in rats. Life Sci. 2006;78(8):851–5. https://doi.org/10.1016/j.lfs.2005.05.085.

    Article  CAS  PubMed  Google Scholar 

  74. Wang Y, Wang Y, Chen G, Li Y, Xu W, Gong S. Quantum-Dot-Based Theranostic Micelles Conjugated with an Anti-EGFR Nanobody for Triple-Negative Breast Cancer Therapy. ACS Appl Mater Interfaces. 2017;9(36):30297–305. https://doi.org/10.1021/acsami.7b05654.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Aswathy J, Seethalekshmy NV, Hiran KR, Bindhu MR, Manzoor K, Nair SV, Menon D. Mn-doped zinc sulphide nanocrystals for immunofluorescent labeling of epidermal growth factor receptors on cells and clinical tumor tissues. Nanotechnol. 2014;25(44):445102. https://doi.org/10.1088/0957-4484/25/44/445102.

    Article  CAS  Google Scholar 

  76. Baselga J. Why the epidermal growth factor receptor? The rationale for cancer therapy. Oncologist. 2002;7:2–8.

    Article  CAS  Google Scholar 

  77. Nguyen PV, Allard-Vannier E, Chourpa I, Herve-Aubert K. Nanomedicines functionalized with anti-EGFR ligands for active targeting in cancer therapy: Biological strategy, design and quality control. Int J Pharm. 2021;605:120795. https://doi.org/10.1016/j.ijpharm.2021.120795.

    Article  CAS  PubMed  Google Scholar 

  78. Rothenberg ML, Carbone DR, Johnson DH. Improving the evaluation of new cancer treatments: challenges and opportunities. Nat Rev Cancer. 2003;3(4):303–9. https://doi.org/10.1038/nrc1047.

    Article  CAS  PubMed  Google Scholar 

  79. Romero Garcia S. Sullivan Lopez Gonzalez J, Luis Baez Viveros J, Aguilar Cazares D, Prado Garcia H. Tumor cell metabolism An integral view. Cancer Biol Ther. 2011;12(11):939–48. https://doi.org/10.4161/cbt.12.11.18140.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Ji TJ, Zhao Y, Ding YP, Nie GJ. Using Functional Nanomaterials to Target and Regulate the Tumor Microenvironment: Diagnostic and Therapeutic Applications. Adv Mater. 2013;25(26):3508–25. https://doi.org/10.1002/adma.201300299.

    Article  CAS  PubMed  Google Scholar 

  81. Oshi MA, Lee J, Naeem M, Hasan N, Kim J, Kim HJ, Lee EH, Jung Y, Yoo JW. Curcumin Nanocrystal/pH-Responsive Polyelectrolyte Multilayer Core-Shell Nanoparticles for Inflammation-Targeted Alleviation of Ulcerative Colitis. Biomacromolecules. 2020;21(9):3571–81. https://doi.org/10.1021/acs.biomac.0c00589.

    Article  CAS  PubMed  Google Scholar 

  82. Yang J, Gao F, Han D, Yang L, Kong X, Wei M, Cao J, Liu H, Wu Z, Pan G. Multifunctional zinc-based hollow nanoplatforms as a smart pH-responsive drug delivery system to enhance in vivo tumor-inhibition efficacy. Mater Des. 2018;139:172–80. https://doi.org/10.1016/j.matdes.2017.11.004.

    Article  CAS  Google Scholar 

  83. Cai X, Luo Y, Zhang W, Du D, Lin Y. pH-Sensitive ZnO quantum dots-doxorubicin nanoparticles for lung cancer targeted drug Delivery. ACS Appl Mater Interfaces. 2016;8(34):22442–50. https://doi.org/10.1021/acsami.6b04933.

    Article  CAS  PubMed  Google Scholar 

  84. Jiang Z, Wang Y, Sun L, Yuan B, Tian Y, Xiang L, Li Y, Li Y, Li J, Wu A. Dual ATP and pH responsive ZIF-90 nanosystem with favorable biocompatibility and facile post-modification improves therapeutic outcomes of triple negative breast cancer in vivo. Biomater. 2019;197:41–50. https://doi.org/10.1016/j.biomaterials.2019.01.001.

    Article  CAS  Google Scholar 

  85. Liang P, Zhang W, Kang T, Wu N, Quan C, Zhang C. Design of pH-sensitive supramolecular assembly for cell targeting and controlled release. J Control Release. 2015;213:e17. https://doi.org/10.1016/j.jconrel.2015.05.024.

    Article  PubMed  Google Scholar 

  86. Zou Y, Yang W, Meng F, Zhong Z. Targeted hepatoma chemotherapy in vivo using galactose-decorated crosslinked pH-sensitive degradable micelles. J Control Release. 2015;213:e125–e6. https://doi.org/10.1016/j.jconrel.2015.05.212.

    Article  PubMed  Google Scholar 

  87. Zhang JM, Chen RE, Chen FQ, Chen MW, Wang YT. Nucleolin targeting AS1411 aptamer modified pH-sensitive micelles: A dual-functional strategy for paclitaxel delivery. J Control Release. 2015;213:E137–E8. https://doi.org/10.1016/j.jconrel.2015.05.232.

    Article  PubMed  Google Scholar 

  88. Min KH, Kim JH, Bae SM, Shin H, Kim MS, Park S, Lee H, Park RW, Kim IS, Kim K, Kwon IC, Jeong SY, Lee DS. Tumoral acidic pH-responsive MPEG-poly(beta-amino ester) polymeric micelles for cancer targeting therapy. J Control Release. 2010;144(2):259–66. https://doi.org/10.1016/j.jconrel.2010.02.024.

    Article  CAS  PubMed  Google Scholar 

  89. Xie J, Zhang Y, Yan C, Song L, Wen S, Zang F, Chen G, Ding Q, Yan C, Gu N. High-performance PEGylated Mn-Zn ferrite nanocrystals as a passive-targeted agent for magnetically induced cancer theranostics. Biomater. 2014;35(33):9126–36. https://doi.org/10.1016/j.biomaterials.2014.07.019.

    Article  CAS  Google Scholar 

  90. Liu Y, Li M, Yang F, Gu N. Magnetic drug delivery systems. Science China-Materials. 2017;60(6):471–86. https://doi.org/10.1007/s40843-017-9049-0.

    Article  CAS  Google Scholar 

  91. Han L, Zhang X-Y, Wang Y-L, Li X, Yang X-H, Huang M, Hu K, Li LH, Wei Y. Redox-responsive theranostic nanoplatforms based on inorganic nanomaterials. J Control Release. 2017;259:40–52. https://doi.org/10.1016/j.jconrel.2017.03.018.

    Article  CAS  PubMed  Google Scholar 

  92. Hu H, Yuan W, Liu F-S, Cheng G, Xu F-J, Ma J. Redox-Responsive Polycation-Functionalized Cotton Cellulose Nanocrystals for Effective Cancer Treatment. ACS Appl Mater Interfaces. 2015;7(16):8942–51. https://doi.org/10.1021/acsami.5b02432.

    Article  CAS  PubMed  Google Scholar 

  93. Xie J, Lee S, Chen XY. Nanoparticle-based theranostic agents. Adv Drug Del Rev. 2010;62(11):1064–79. https://doi.org/10.1016/j.addr.2010.07.009.

    Article  CAS  Google Scholar 

  94. Wang J, Hu Y, Chen J, Ye C. Self-assembledCeVO4/Au heterojunction nanocrystals for photothermal/photoacoustic bimodal imaging-guided phototherapy. RSC Adv. 2020;10(5):2581–8. https://doi.org/10.1039/c9ra09860g.

  95. Wang S, Mao J, Liu H, Huang S, Cai J, Gui W, Wu J, Xu J, Shen J, Wang Z. pH-Sensitive nanotheranostics for dual-modality imaging guided nanoenzyme catalysis therapy and phototherapy. J Mater Chem B. 2020;8(22):4859–69. https://doi.org/10.1039/c9tb02731a.

    Article  CAS  PubMed  Google Scholar 

  96. Zhu HB, Li YX, Qiu RQ, Shi L, Wu WT, Zhou SQ. Responsive fluorescent Bi2O3@PVA hybrid nanogels for temperature-sensing, dual-modal imaging, and drug delivery. Biomater. 2012;33(10):3058–69. https://doi.org/10.1016/j.biomaterials.2012.01.003.

    Article  CAS  Google Scholar 

  97. Tuomela A, Liu P, Puranen J, Ronkko S, Laaksonen T, Kalesnykas G, et al. Brinzolamide nanocrystal formulations for ophthalmic delivery: reduction of elevated intraocular pressure in vivo. Int J Pharm. 2014;467(1-2):34–41. https://doi.org/10.1016/j.ijpharm.2014.03.048.

    Article  CAS  PubMed  Google Scholar 

  98. Tuomela A, Hirvonen J, Peltonen L. Stabilizing Agents for Drug Nanocrystals: Effect on Bioavailability. Pharmaceutics. 2016;8(2):18. https://doi.org/10.3390/pharmaceutics8020016.

    Article  CAS  Google Scholar 

  99. Sun W, Tian W, Zhang Y, He J, Mao S, Fang L. Effect of novel stabilizers-cationic polymers on the particle size and physical stability of poorly soluble drug nanocrystals. Nanomed-Nanotechnol Biol Med. 2012;8(4):460–7. https://doi.org/10.1016/j.nano.2011.07.006.

    Article  CAS  Google Scholar 

  100. Kabanov AV, Batrakova EV, Alakhov VY. Pluronic((R)) block copolymers for overcoming drug resistance in cancer. Adv Drug Del Rev. 2002;54(5):759–79. https://doi.org/10.1016/s0169-409x(02)00047-9.

    Article  CAS  Google Scholar 

  101. Liu HZ, Ma Y, Liu D, Fallon JK, Liu F. The Effect of Surfactant on Paclitaxel Nanocrystals: An In Vitro and In Vivo Study. J Biomed Nanotechnol. 2016;12(1):147–53. https://doi.org/10.1166/jbn.2016.2127.

    Article  CAS  PubMed  Google Scholar 

  102. Wang S, Wang H, Liu Z, Wang L, Wang X, Su L, Chang J. Smart pH- and reduction-dual-responsive folate-PEG-coated polymeric lipid vesicles for tumor-triggered targeted drug delivery. Nanoscale. 2014;6(13):7635–42. https://doi.org/10.1039/c4nr00843j.

    Article  CAS  PubMed  Google Scholar 

  103. Kanamala M, Palmer BD, Wilson WR, Wu ZM. Characterization of a smart pH-cleavable PEG polymer towards the development of dual pH-sensitive liposomes. Int J Pharm. 2018;548(1):288–96. https://doi.org/10.1016/j.ijpharm.2018.07.009.

    Article  CAS  PubMed  Google Scholar 

  104. Suma T, Miyata K, Anraku Y, Watanabe S, Christie RJ, Takemoto H, Shioyama M, Gouda N, Ishii T, Nishiyama N, Kataoka K. Smart Multilayered Assembly for Biocompatible siRNA Delivery Featuring Dissolvable Silica, Endosome-Disrupting Polycation, and Detachable PEG. Acs Nano. 2012;6(8):6693–705. https://doi.org/10.1021/nn301164a.

    Article  CAS  PubMed  Google Scholar 

  105. Li H, Miteva M, Kirkbride KC, Cheng MJ, Nelson CE, Simpson EM, Gupta MK, Duvall CL, Giorgio TD. Dual MMP7-Proximity-Activated and Folate Receptor-Targeted Nanoparticles for siRNA Delivery. Biomacromolecules. 2015;16(1):192–201. https://doi.org/10.1021/bm501394m.

    Article  CAS  PubMed  Google Scholar 

  106. Razzazan A, Atyabi F, Kazemi B, Dinarvand R. Influence of PEG Molecular Weight on the Drug Release and In vitro Cytotoxicity of Single-Walled Carbon Nanotubes-PEG-Gemcitabine Conjugates. Curr Drug Del. 2016;13(8):1313–24. https://doi.org/10.2174/1567201813666160111123947.

    Article  CAS  Google Scholar 

  107. Du XJ, Wang JL, Liu WW, Yang JX, Sun CY, Sun R, et al. Regulating the surface poly(ethylene glycol) density of polymeric nanoparticles and evaluating its role in drug delivery in vivo. Biomater. 2015;69:1–11. https://doi.org/10.1016/j.biomaterials.2015.07.048.

    Article  CAS  Google Scholar 

  108. Wu B, Zhang LJ, Zhang CJ, Deng K, Ao YW, Mei H, Zhou W, Wang CX, Yu H, Huang SW. Effect of Poly(ethylene glycol) (PEG) Surface Density on the Fate and Antitumor Efficacy of Redox-Sensitive Hybrid Nanoparticles. ACS Biomater Sci Eng. 2020;6(7):3975–83. https://doi.org/10.1021/acsbiomaterials.0c00516.

    Article  CAS  PubMed  Google Scholar 

  109. Marruecos DF, Kastantin M, Schwartz DK, Kaar JL. Dense Poly(ethylene glycol) Brushes Reduce Adsorption and Stabilize the Unfolded Conformation of Fibronectin. Biomacromolecules. 2016;17(3):1017–25. https://doi.org/10.1021/acs.biomac.5b01657.

    Article  CAS  Google Scholar 

  110. Hou WM, Miyazaki S, Takada M, Komai T. Sustained release of indomethacin from chitosan granules. Chem Pharm Bull (Tokyo). 1985;33(9):3986–92.

    Article  CAS  Google Scholar 

  111. Miyazaki S, Ishii K, Nadai T. The use of chitin and chitosan as drug carriers. Chem Pharm Bull (Tokyo). 1981;29(10):3067–9.

    Article  CAS  Google Scholar 

  112. Miyazaki S, Yamaguchi H, Yokouchi C, Takada M, Hou WM. Sustained release of indomethacin from chitosan granules in beagle dogs. J Pharm Pharmacol. 1988;40(9):642–3. https://doi.org/10.1111/j.2042-7158.1988.tb05325.x.

    Article  CAS  PubMed  Google Scholar 

  113. Quan P, Shi K, Piao H, Piao H, Liang N, Xia D, Cui F. A novel surface modified nitrendipine nanocrystals with enhancement of bioavailability and stability. Int J Pharm. 2012;430(1-2):366–71. https://doi.org/10.1016/j.ijpharm.2012.04.025.

    Article  CAS  PubMed  Google Scholar 

  114. Moghaddam AS, Khonakdar HA, Sarikhani E, Jafari SH, Javadi A, Shamsi M, Amirkhani MA, Ahadian S. Fabrication of Carboxymethyl Chitosan Nanoparticles to Deliver Paclitaxel for Melanoma Treatment. ChemNanoMat. 2020;6(9):1373–85. https://doi.org/10.1002/cnma.202000229.

    Article  CAS  Google Scholar 

  115. Paiva D, Ivanova G. Pereira MdC, Rocha S. Chitosan conjugates for DNA delivery. Phys Chem Chem Phys. 2013;15(28):11893–9. https://doi.org/10.1039/c3cp51215k.

    Article  CAS  PubMed  Google Scholar 

  116. Sahariah P, Masson M. Antimicrobial Chitosan and Chitosan Derivatives: A Review of the Structure-Activity Relationship. Biomacromolecules. 2017;18(11):3846–68. https://doi.org/10.1021/acs.biomac.7b01058.

    Article  CAS  PubMed  Google Scholar 

  117. Pandey N, Soto-Garcia LF, Liao J, Zimmern P, Nguyen KT, Hong Y. Mussel-inspired bioadhesives in healthcare: design parameters, current trends, and future perspectives. Biomater Sci. 2020;8(5):1240–55. https://doi.org/10.1039/c9bm01848d.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Jiang J, Zhu L, Zhu L, Zhu B, Xu Y. Surface Characteristics of a Self-Polymerized Dopamine Coating Deposited on Hydrophobic Polymer Films. Langmuir. 2011;27(23):14180–7. https://doi.org/10.1021/la202877k.

    Article  CAS  PubMed  Google Scholar 

  119. Kang SM, Hwang NS, Yeom J, Park SY, Messersmith PB, Choi IS, Langer R, Anderson DG, Lee H. One-Step Multipurpose Surface Functionalization by Adhesive Catecholamine. Adv Funct Mater. 2012;22(14):2949–55. https://doi.org/10.1002/adfm.201200177.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Zhan H, Jagtiani T, Liang JF. A new targeted delivery approach by functionalizing drug nanocrystals through polydopamine coating. Eur J Pharm Biopharm. 2017;114:221–9. https://doi.org/10.1016/j.ejpb.2017.01.020.

    Article  CAS  PubMed  Google Scholar 

  121. Hao YN, Zheng AQ, Guo TT, Shu Y, Wang JH, Johnson O, Chen W. Glutathione triggered degradation of polydopamine to facilitate controlled drug release for synergic combinational cancer treatment. J Mater Chem B. 2019;7(43):6742–50. https://doi.org/10.1039/c9tb01400d.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Yurkin ST, Wang Z. Cell membrane-derived nanoparticles: emerging clinical opportunities for targeted drug delivery. Nanomedicine. 2017;12(16):2007–19. https://doi.org/10.2217/nnm-2017-0100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Li RX, He YW, Zhang SY, Qin J, Wang JX. Cell membrane-based nanoparticles: a new biomimetic platform for tumor diagnosis and treatment. Acta Pharm Sin B. 2018;8(1):14–22. https://doi.org/10.1016/j.apsb.2017.11.009.

    Article  PubMed  Google Scholar 

  124. Su J, Sun H, Meng Q, Yin Q, Tang S, Zhang P, Chen Y, Zhang Z, Yu H, Li Y. Long Circulation Red-Blood-Cell-Mimetic Nanoparticles with Peptide-Enhanced Tumor Penetration for Simultaneously Inhibiting Growth and Lung Metastasis of Breast Cancer. Adv Funct Mater. 2016;26(8):1243–52. https://doi.org/10.1002/adfm.201504780.

    Article  CAS  Google Scholar 

  125. Rao L, Meng QF, Bu LL, Cai B, Huang Q, Sun ZJ, Zhang WF, Li A, Guo SS, Liu W, Wang TH, Zhao XZ. Erythrocyte Membrane-Coated Upconversion Nanoparticles with Minimal Protein Adsorption for Enhanced Tumor Imaging. ACS Appl Mater Interfaces. 2017;9(3):2159–68. https://doi.org/10.1021/acsami.6b14450.

    Article  CAS  PubMed  Google Scholar 

  126. Zhu DM, Xie W, Xiao YS, Suo M, Zan MH, Liao QQ, Hu XJ, Chen LB, Chen B, Wu WT, Ji LW, Huang HM, Guo SS, Zhao XZ, Liu QY, Liu W. Erythrocyte membrane-coated gold nanocages for targeted photothermal and chemical cancer therapy. Nanotechnol. 2018;29(8):084002. https://doi.org/10.1088/1361-6528/aa9ca1.

    Article  CAS  Google Scholar 

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Funding

This study was supported by National Natural Science Foundation of China (No. 22078234).

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Authors and Affiliations

  1. Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, China

    Meng Bai & Zhenping Wei

  2. Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark

    Mingshi Yang

  3. State Key Lab Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China

    Junbo Gong

  4. School of Pharmacy, Shenyang Pharmaceutical University, Benxi, 117004, China

    Hui Xu

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  1. Meng Bai
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  2. Mingshi Yang
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  3. Junbo Gong
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  4. Hui Xu
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  5. Zhenping Wei
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Contributions

Conceptualization: Meng Bai, Zhenping Wei; Formal analysis: Meng Bai; Writing - Review & Editing: Meng Bai; Supervision: Zhenping Wei, Mingshi Yang, Junbo Gong; Project administration: Zhenping Wei; Funding acquisition: Junbo Gong. All authors contributed to the final version of the manuscript.

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Bai, M., Yang, M., Gong, J. et al. Progress and Principle of Drug Nanocrystals for Tumor Targeted Delivery. AAPS PharmSciTech 23, 41 (2022). https://doi.org/10.1208/s12249-021-02200-w

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