Chemoresistance and hence the consequent treatment failure is considerably challenging in clinical cancer therapeutics. The understanding of the genetic variations in chemoresistance acquisition encouraged the use of gene modulatory approaches to restore anti-cancer drug efficacy. Many smart nanoparticles are designed and optimized to mediate combinational therapy between nucleic acid and anti-cancer drugs. This review aims to define a rational design of such co-loaded nanocarriers with the aim of chemoresistance reversal at various cellular levels to improve the therapeutic outcome of anticancer treatment. Going through the principles of therapeutics loading, physicochemical characteristics tuning, and different nanocarrier modifications, also looking at combination effectiveness on chemosensitivity restoration. Up to now, these emerging nanocarriers are in development status but are expected to introduce outstanding outcomes.
Keywords: 5-FU, 5-Flurouracil; ABCB, ATP Binding Cassette Subfamily B Member; AIF, Apoptosis-inducing factor; AKT, Serine/threonine kinase; ASGPR, The asialoglycoprotein receptor; ASO, Antisense oligonucleotides; Anti-cancer drugs; BBB, Blood-brain barrier; BCRP, Breast cancer-resistant protein; Bak, Bcl2-antagonist/killer; Bax, Bcl-2-associated X protein apoptotic activator; Bcl-2, B-cell lymphoma 2; Bcl-xl, B-cell lymphoma-extra large; CAV-1, Caveolin 1; CDK, Cyclin-dependent kinase; CI, Combination index; CMD, Carboxymethyl dextran; CPT, Camptothecin; CSCs, Cancer stem cells; CT, The computed tomography; ChNPs, Chitosan nanoparticles; Chemoresistance reversal; CisPt, Cisplatin; Combination therapy; DMSO, Dimethyl sulfoxide; DOPE, Dioleoylphosphatidylethanolamine; DOTAP, 1,2-Dioleoyl-3-trimethylammonium propane; DOX, Doxorubicin; DSPE, 1,2-Distearoyl-sn-glycerol-3-phosphoethanolamine; DTX, Docetaxel; E-CAD, E-cadherin; EC50, The half maximal effective concentration; EGFR, Epidermal growth factor receptor; EPR, The enhanced permeability and retention; ERK, Extracellular regulated kinase; EZH2, Enhancer Of Zeste 2 Polycomb Repressive Complex 2 Subunit; FAK, Focal adhesion kinase; FRα, Folate receptor-α; GEM, Gemcitabine; GSH, Glutathione; GalNAc, N-acetylgalactosamine; GnRH, Gonadotropin-releasing hormone; H1F1, Hypoxia-inducible factor 1; HRAS, GTPase HRas enzyme; IC50, The half-maximal inhibitory concentration; IL-17B, Interleukin 17B; ILK, Integrin-linked kinase; Kras, Kirsten rat sarcoma GTPase enzyme; LDL, Low-density lipoprotein; LHRH, Luteinizing hormone-releasing hormone; LHSSG2C, Ditetradecyl 2-(4-(2-(2-(2-(2-(2,6-diaminohexanamido)-3-(1H-imidazole-4-yl) propanamido) ethyl) disulfanyl) ethylamino)-4-oxobutanamido) pentanedioate; LRP, Lung resistant protein; MAPK, Mitogen-activated protein kinase; MDM, Mixed dendrimer micelles; MDR, Multidrug-resistant; MRI, Magnetic resonance images; MSNRs, Mesoporous silica nanorods; MTDH, Metadherin; MTT, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; MVP, Major vault protein; NF-κB, Nuclear factor-kappa light chain enhancer of activated B cells; Nanoparticles; Notch-1, Notch homolog 1, translocation-associated; Nucleic acids; OEI, Oligoethylenimine; ORF, Open reading frame; OxaPt, Oxaliplatin; P-gp, P-glycoprotein; PAH, Poly (acrylhydrazine); PAMAM, Polyamidoamine; PBS, Phosphate Buffered Saline; PDMAPMA, Poly (3-dimethylaminopropyl methacrylamide); PDX, Patient-derived xenograft; PEG, Polyethylene glycol; PEI, Polyethyleneimine; PI3-kinase, Phosphatidylinositol 3′-kinase; PLA, Polylactic acid; PLGA, Poly (lactic-co-glycolic acid); PTEN, Phosphatase and tensin homolog; PTK-1, Protein tyrosine kinase 1; PTX, Paclitaxel; Polζ, Translesion DNA polymerase; Q, Combination efficacy; R, Resistance index; RES, Reticuloendothelial system; REV, Reversionless phenotype; RGD, The tripeptide arginine−glycine−aspartic sequence; RISC, RNA Induced Silencing Complex; Rac1, Ras-related C3 botulinum toxin substrate 1; SIP-1, Stress-induced protein 1; SLN, Solid lipid nanoparticles; SR-BI, Scavenger receptor class B type I; SSRTs, Somatostatin receptors; STAT-3, Signal transducer and activator of transcription 3; TGN, Brain targeting peptide; TIMP3, Tissue inhibitor of metalloproteinase 3; TLR4, Toll-like receptor 4; TLS, Translesion synthesis; TRAIL, Tumor necrosis factor (TNF)-related apoptosis-inducing ligand; USP9X, Ubiquitin specific peptidase 9, X-linked; VEGF, Vascular endothelial growth factor; ZEB, Zinc finger E-box-binding homeobox 1 transcription factor; c-Myc, C-Master regulator of cell cycle entry, proliferative and metabolism; miRNA, Micro ribonucleic acid; p27Kip1, Cell cycle inhibitor; pAKT, Phosphatidylinositol 3-kinase and Protein Kinase; pDNA, Plasmid deoxyribonucleic acid; shRNA, Short hairpin ribonucleic acid; siRNA, Small interfering ribonucleic acid.
© 2022 The Authors. Published by Elsevier B.V.