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Targeted Drug Delivery for Chronic Lymphocytic Leukemia

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Abstract

Chronic lymphocytic leukemia (CLL) still represents an incurable disorder that may progress to other more aggressive types of cancer despite the available therapy and the development that has been reached in the immunophenotypic and mutational status characterization of CLL. Hence, innovative therapeutics strategies are required together with the advancement in chemo-immunotherapy and targeted treatments. Parallelly, more focus should be put on the drug delivery process to improve the effectiveness/toxicity ratio of both conventional and new drugs and reduce the risk of drug resistance. In the present review, different types of nanocarriers that can be harnessed against CLL, their features, their capabilities in targeting CLL cells, and the latest relevant data are discussed. We provide an integral description of each nanocarrier, including lipidic, polymeric, and inorganic carriers, aiming to offer a constructive resource for the rational design of potential nanomedicines to advance the fight against CLL.

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Abbreviations

ABC:

Accelerated blood clearance

ACS:

American cancer society

ADCC:

Antibody-dependent cellular cytotoxicity

AMOs:

Anti-miRNA oligonucleotides

APRIL:

A proliferation-inducing ligand

APTES:

3-Aminopropyl triethoxysilane

BAFF:

B-cell activating factor

BAFFR:

B-cell activating factor receptor

BCL-2:

B-cell lymphoma 2

BCMA:

B-cell maturation antigen

BCR:

B-cell receptor

BDM:

Bendamustine

BM:

Bone marrow

BTK:

Bruton tyrosine kinase

CD:

Cyclodextrin

CDC:

Complement-dependent cytotoxicity

cdk6:

Cyclin-dependent kinase 6

Chol:

Cholesterol

CLL:

Chronic lymphocytic leukemia

CPNPs:

Calcium phosphate nanoparticles

CXCL12/CXCL13:

C-X-C motif chemokine ligand 12/13

CXCR4/CXCR5:

C-X-C motif chemokine receptor type 4/5

DDS:

Drug delivery system;

Dlin-MC3-DMA:

Dilinoleylmethyl-4-dimethylaminobutyrate

DMG-PEG:

1,2-Dimyristoyl-sn-glycerol, methoxypolyethylene glycol

DMPG:

1,2-Dimyristoyl-sn-glycero-3-phospho-(19-rac-glycerol)

DMPS:

1,2-Dimyristoyl- sn-glycero-3-phospho-L-serine

DMSA:

3-Dimercaptosuccinic acid

DODAP:

1,2-Dioleyl-3-trimethyl ammonium- propane

DOPC:

1,2-Dioleoyl-sn-glycero-3-phosphocholine

DOPE:

1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine

Dox:

Doxorubicin

DS:

Dense shell

DSPC:

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

DSPE-PEG:

N-palmitoyl-sphingosine-1- succinylpolyethylene glycol

DSPG:

Distearoylphosphatidylglycerol

DSPS:

Distearoyl phosphatidylserine

EPR:

Enhanced permeability and retention

FA:

Fludarabine

FDA:

US Food and Drug Administration

G4:

4Th generation

GMS:

Glyceryl monostearate

GNPs:

Gold nanoparticles

GLUTs:

Glucose transporters

HA:

Hyaluronic acid

HDL:

High-density lipoprotein

IBR:

Ibrutinib

IGHV:

Immunoglobulin heavy-chain genes

ILNPs:

Ionizable lipid nanoparticles

ILPs:

Immunoliposomes

IONPs:

Iron oxide nanoparticles

LNs:

Lymph nodes

LPs:

Liposomes

MABs:

Monoclonal antibodies

Mal:

Maltose

Mal-3:

Maltotriose

Mcl-1:

Myeloid cell leukemia-1

miRNA:

MicroRNA

MRI:

Magnetic resonance imaging

MS4A1:

Membrane spanning 4-domains A1

MSNPs:

Mesoporous silica nanoparticles

NLC:

Nurse-like cell

NPs:

Nanoparticles

NSLCs:

Nanostructured lipid carriers

NTs:

Nucleoside transporters

OS:

Open shell

PAMAM:

Polyamidoamine

PBMCs:

Peripheral blood mononuclear cells

PCL:

Polycaprolactone

PDI:

Polydispersity index

PEG:

Polyethylene glycol

PGA:

Polyglycolic acid;

PGMC:

Propylene glycol monocaprylate

PI3Ks:

Phosphoinositol-3-kinases

PLA:

Polylactic acid

PLGA:

Poly(lactic acid-co-glycolic acid)

PPI:

Polypropyleneimine

RES:

Reticuloendothelial system

ROR1:

Receptor tyrosine kinase orphan receptor 1

ROS:

Reactive oxygen species

RTX:

Rituximab

SBE-b-CD:

Sulfobutylether-b-cyclodextrin

SEER:

Surveillance, epidemiology, and end result

sHDL:

Synthetic high-density lipoprotein

siRNA:

Small interfering RNA

SR-B1:

Scavenger receptor type B-1

STAT3:

Signal transducer and activator of transcription 3

TACI:

Transmembrane activator and calcium modulator and cyclophin ligand interactor

TRAIL:

Tumor necrosis factor-related apoptosis-inducing ligand

TrxR:

Thioredoxin reductase

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ACKNOWLEDGMENTS AND DISCLOSURES

This study was supported by the National Natural Science Foundation of China (Nos. 81872823, and 82073782), the Shanghai Science and Technology Committee (No. 19430741500), the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of Traditional Chinese Medicine (zdsys-202103, China). The authors declare no conflicts of interest.

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  1. Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, China

    Makhloufi Zoulikha & Wei He

  2. Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, 200443, China

    Wei He

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Zoulikha, M., He, W. Targeted Drug Delivery for Chronic Lymphocytic Leukemia. Pharm Res 39, 441–461 (2022). https://doi.org/10.1007/s11095-022-03214-0

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