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Clinical Trials Involving Chemotherapy-Based Nanocarriers in Cancer Therapy: State of the Art and Future Directions

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Cancer Nanotechnology

Abstract

Despite significant achievements in cancer treatment, it remains a challenging burden, and there is limited success in the clinical therapy. In recent years, progress in nanotechnology provides plenty of tools to counteract cancer with innovative nanomedicines that can be exploited in intracellular drug delivery. Specifically, the design and development of nanomaterials, such as nanoparticles and hydrogels, aim at achieving smart nanosystems with great multifunctionality and therapeutic potential. In this context, advances in tailored biomaterials for drug delivery as cancer treatment include new strategies to overcome the obstacles and limitations usually encountered with traditional therapeutic agents, thereby reducing the lack of selectivity and side effects. Hence, a big effort is being invested in designing and developing more accurate strategies toward personalized medicine, which has emerged as a promising therapeutic approach with a wide potential to increase treatment outcomes and patient survival. In this chapter, we provide a comprehensive analysis and discuss the development of advanced nanocarriers involving chemotherapeutic agents in clinical trials against multiple types of cancer. We also focus on some reasons that could explain why some treatments fail in clinics.

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Abbreviations

AIDS:

Acquired immune deficiency syndrome;

ALL:

Lymphoblastic leukemia;

ARC:

International Agency for Research on Cancer;

AUC:

Area under the curve;

AuNPs:

Gold nanoparticles;

BBB:

Blood-brain barrier;

CAFs:

Cancer-associated fibroblasts

CD:

Cyclodextrin

CD-PEG:

Cyclodextrin-polyethylene glycol

Chol:

Cholesterol

DMPC:

1,2-Dimyris-toyl-sn-glycero-3-phosphocholine

DMPG:

1,2-Dimyristoyl-sn-glycero-3-phospho-(1’-racglycerol)

DNA:

Deoxyribonucleic acid

DOPC:

Palmitoyloleoylphosphatidylcholine

DOPS:

Dioleoylphosphatidylserine

DOTAP:

1,2-Dioleoyl-3-trimethylammonium propane

DPPC:

Dipalmitoylphosphatidylcholine

DPPG:

1,2-Dipalmitoyl-sn-glycero-3-phosphoglycerol;

DSPC:

Distearoylphosphatidylcholine

DSPE:

Distearoyl-sn-glycero-phosphoethanolamine

DSPG:

1,2-Distearoyl-sn-glycero-3-phosphoglycerol

ECM:

Extracellular matrix

EGFR:

Epidermal growth factor receptor

EMA:

European Medicines Agency

EPC:

Egg phosphatidylcholine

EPR:

Enhanced permeability and retention

FDA:

US Food and Drug Administration

HCC:

Hepatocellular carcinoma

HER2:

Human epidermal growth factor receptor 2

HIV:

Human immunodeficiency virus

HSA:

Human serum albumin

HSPC:

Hydrogenated soy phosphatidylcholine

KRAS:

Kirsten rat sarcoma viral oncogene homolog

KS:

Kaposi sarcoma

L-MTP-PE:

Muramyl tripeptide phosphatidylethanolamine

LNPs:

Lipid nanoparticles

LSAM:

Large surface area microparticle

MDP:

Muramyl dipeptide

MDR:

Multidrug resistance

MPEG:

Methoxy polyethylene glycol

MPPE:

Maleimidated palmitoyl phosphatidylethanolamine

MSPC:

1-Myristoyl-2-stearoyl-sn-glycero-3-phosphocholine

NGPE:

N-glutaryl phosphatidylethanolamine

NIPAM:

Poly(N-isopropylacrylamide)

NPs:

Nanoparticles

NSCLC:

Non-small cell lung cancer

PC:

Phosphatidylcholine

PE:

Polyethylene

PEG:

Polyethylene glycol

PEG2000-DSPE:

PEGylated distearoyl-sn-glycero-phosphoethanolamine

PFS:

Progression-free survival

PICN:

Paclitaxel injection concentrate for nanodispersion

PLA:

Polylactic acid

PLA2:

Phospholipase A2

PLGA:

Polylactide-co-glycolic acid

POPC:

Palmitoyloleoylphosphatidylcholine

PPE:

Palmar-plantar erythrodysesthesia

PSMA:

Prostate-specific membrane antigen

PVP:

Polyvinyl-pyrrolidone

RES:

Reticuloendothelial system

RFA:

Radiofrequency ablation

RNA:

Ribonucleic acid

SM:

Sphingomyelin

SPARC:

Sun Pharma Advanced Research Company, Ltd.

TAMs:

Tumor-associated macrophages

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Acknowledgments

Marco Cordani is currently a recipient of a Maria Zambrano research contract from the Spanish Ministry of Universities and Complutense University of Madrid (call of grants for the requalification of the Spanish university system 2021–2023). Marco Cordani acknowledges support of the Recovery, Transformation, and Resilience Plan “Next generation EU”. Raffaele Strippoli acknowledges a grant form Ministry for Health of Italy (Ricerca Corrente).

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Author notes

  1. Tania B. Lopez-Mendez and Raffaele Strippoli contributed equally with all other contributors.

Authors and Affiliations

  1. PharmaMar S.A., Colmenar Viejo, Madrid, Spain

    Tania B. Lopez-Mendez & Pilar Calvo

  2. Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy

    Raffaele Strippoli & Flavia Trionfetti

  3. National Institute for Infectious Diseases L. Spallanzani IRCCS, Rome, Italy

    Raffaele Strippoli & Flavia Trionfetti

  4. Department of Biochemistry and Molecular Biology, School of Biology, Complutense University, Madrid, Spain

    Marco Cordani

  5. Instituto de Investigaciones Sanitarias San Carlos (IdISSC), Madrid, Spain

    Marco Cordani

  6. Molecular Imaging Innovations Institute (MI3), Department of Radiology, Weill Cornell Medicine, New York, NY, USA

    Juan Gonzalez-Valdivieso

Authors
  1. Tania B. Lopez-Mendez
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  2. Raffaele Strippoli
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  3. Flavia Trionfetti
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  4. Pilar Calvo
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  5. Marco Cordani
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  6. Juan Gonzalez-Valdivieso
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Corresponding authors

Correspondence to Marco Cordani or Juan Gonzalez-Valdivieso .

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Editors and Affiliations

  1. University of Beira Interior, CICS-UBI – Health Sciences Research Centre, Covilhã, Portugal

    Ângela Maria Almeida de Sousa

  2. School of Pharmaceutical Sciences, São Paulo State University, São Paulo, Brazil

    Christiane Pienna Soares

  3. School of Pharmaceutical Sciences, São Paulo State University, São Paulo, Brazil

    Marlus Chorilli

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Lopez-Mendez, T.B., Strippoli, R., Trionfetti, F., Calvo, P., Cordani, M., Gonzalez-Valdivieso, J. (2023). Clinical Trials Involving Chemotherapy-Based Nanocarriers in Cancer Therapy: State of the Art and Future Directions. In: Almeida de Sousa, Â.M., Pienna Soares, C., Chorilli, M. (eds) Cancer Nanotechnology. Springer, Cham. https://doi.org/10.1007/978-3-031-17831-3_12

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