Nanocarrier drug resistant tumor interactions: novel approaches to fight drug resistance in cancer

Abstract

Cancer is one of the biggest healthcare concerns in our century, a disease whose treatment has become even more difficult following reports of drug-resistant tumors. When this happens, chemotherapy treatments fail or decrease in efficiency, leading to catastrophic consequences to the patient. This discovery, along with the fact that drug resistance limits the efficacy of current treatments, has led to a new wave of discovery for new methods of treatment. The use of nanomedicine has been widely studied in current years as a way to effectively fight drug resistance in cancer. Research in the area of cancer nanotechnology over the past decades has led to tremendous advancement in the synthesis of tailored nanoparticles with targeting ligands that can successfully attach to chemotherapy-resistant cancer by preferentially accumulating within the tumor region through means of active and passive targeting. Consequently, these approaches can reduce the off-target accumulation of their payload and lead to reduced cytotoxicity and better targeting. This review explores some categories of nanocarriers that have been used in the treatment of drug-resistant cancers, including polymeric, viral, lipid-based, metal-based, carbon-based, and magnetic nanocarriers, opening the door for an exciting field of discovery that holds tremendous promise in the treatment of these tumors.

Keywords: Drug-resistance; cancer; drug delivery; nanocarriers; nanotechnology.

Figure 1

Tumor heterogeneity evolution (a) linear or (b) branched (A)^[20]; Epithelial-mesenchymal transition mechanism (B)^[23]

Figure 2

A graphical representation of NP-assisted cancer-killing effects. NP: nanoparticle; EPR: enhanced permeability

Figure 3

Schematic representation of polymeric micelle and reverse polymeric micelle (Original figure) (A); Schematic representation of a dendrimer (B)^[38]; Schematic representation of possible types of drug-dendrimer interactions (C)^[38]; Schematic representation of liposomes (left) versus polymersomes (right) (D)^[47]

Figure 4

Tobacco mosaic virus (TMV) delivery of Pt in platinum-resistant ovarian cancer cells (A)^[58]; DOX delivery in gH625 Herpes virus derived-protein encapsulated liposome in drug-resistant lung adenocarcinoma cells (B)^[59]; Western reverse (WR) vaccinia targeting PGE2 to overcome immunotherapy resistant cancer cells (C)^[61]

Figure 5

Schematic representation of the different types of liposomal drug delivery systems. Conventional liposome (a), PEGylated liposome (b), Ligand-targeted liposome (c), Theragnostic liposome (d)^[72] (A); Schematic representation of the different types of liposomes^[67] (B); Schematic representation of liposome-based drug delivery system for cancer therapy^[68] (C); Schematic illustration for triggered release of hypoxia-responsive liposomal drug delivery system (D)^[196]

Figure 6

Schematic representation of the SLNs structure, representing the solid lipid matrix, surfactant, and co-surfactant^[83] (A); Classification of three types of classical SLNs including drug-enriched shell, drug-enriched core, and solid solution^[85] (B); Images of spheroids formation in different period of time with respective size (μm). MCF-7/ADR (a), NCI/ADR (b). Images are representative of triplicate samples^[93] (C); Development of fucose decorated methotrexate loaded SLNs (D). The proposed mechanism of action is methotrexate via ligand-receptor mediated endocytosis and internalization^[96]

Figure 7

Schematic representation of various hybridizations of carbon, together with their corresponding allotropes. Note, for simplification, CNTs and Fullerenes are presented as sp² carbons. *Denotes transitional hybridization between 2-3

Figure 8

Selected properties of carbon-based nanomaterials that constitute for their popularity in the field of nanomedicine-based anticancer therapy^[,,,]

Figure 9

Examples of strategies used to bond more than one bioactive molecule to the CNMs. Covalent bonding of polyethylenimine and aptamers to the surface of PEG-modified CNTs, combined with non-covalent π-π stacking of DOX^[138] (A); covalent bonding of cRGD combined with the loading of DOX into the CNMs’ cavity for selective targeting of cancer cells^[135] (B); combination of covalent and non-covalent binding of a single drug for the controllable release from graphene quantum dots^[167] (C); manganese ferrite grown on the surface of graphene oxide, followed by modification with a radioisotope via electrophilic substitution and π-π stacking of DOX^[143] (D); two anticancer drugs, bonded to the surface of graphene via covalent (Pt) and non-covalent (DOX) interactions for an enhanced anticancer effect^[142] (E)

Figure 10

Examples of efficient targeting of tumors in vivo, with the aid of CNMs. Size reduction (A and B) and complete tumor eradication (C and D) can be observed. The materials are (A) carbon nanoparticles^[135], (B) GO^[183], (C) carbon nanozyme^[139], and (D) CNTs^[191]