Nanostructures for site-specific delivery of oxaliplatin cancer therapy: Versatile nanoplatforms in synergistic cancer therapy

Abstract

As a clinically approved treatment strategy, chemotherapy-mediated tumor suppression has been compromised, and in spite of introducing various kinds of anticancer drugs, cancer eradication with chemotherapy is still impossible. Chemotherapy drugs have been beneficial in improving the prognosis of cancer patients, but after resistance emerged, their potential disappeared. Oxaliplatin (OXA) efficacy in tumor suppression has been compromised by resistance. Due to the dysregulation of pathways and mechanisms in OXA resistance, it is suggested to develop novel strategies for overcoming drug resistance. The targeted delivery of OXA by nanostructures is described here. The targeted delivery of OXA in cancer can be mediated by polymeric, metal, lipid and carbon nanostructures. The advantageous of these nanocarriers is that they enhance the accumulation of OXA in tumor and promote its cytotoxicity. Moreover, (nano)platforms mediate the co-delivery of OXA with drugs and genes in synergistic cancer therapy, overcoming OXA resistance and improving insights in cancer patient treatment in the future. Moreover, smart nanostructures, including pH-, redox-, light-, and thermo-sensitive nanostructures, have been designed for OXA delivery and cancer therapy. The application of nanoparticle-mediated phototherapy can increase OXA's potential in cancer suppression. All of these subjects and their clinical implications are discussed in the current review.

Keywords: Chemoresistance; Gene and drug delivery; Oxaliplatin; Synergistic cancer therapy; Targeted delivery.

Graphical abstract

Fig. 1

The role of nanostructures for delivery of chemotherapy drugs. The nanocarriers can utilize multiple methods for the suppression of cancer. The nanoparticles can improve the internalization of current chemotherapy drugs to accelerate tumor suppression. Moreover, nanoparticles mediate co-delivery of chemotherapy drugs and genes in synergistic cancer therapy. Even the anti-tumor immune responses including increase in the number of CD4+ and CD8+ T cells can be induced by nanocarriers. Moreover, nanoparticles respond to certain stimuli in tumor microenvironment including pH and their functionalization with ligands and peptides such as cRGD can improve potential in targeting cancer cells and inducing DNA damage.

Fig. 2

The delivery of OXA and also co-delivery in cancer chemotherapy. The targeted delivery of OXA can enhance activity and infiltration of T cells to augment the anti-cancer immune responses. The chitosan-based nanoparticles can release chitosan and ascorbic acid in response to pH for cancer removal. Moreover, PLGA/PHBV nanoparticles respond to ROS to induce apoptosis after OXA release. The co-delivery of OXA with other kinds of drugs such as gemcitabine and 5-flourouracil by nanoparticles has been evaluated in cancer therapy. The functionalization of nanoparticles with folic acid increases their potential in targeted delivery of drugs.

Fig. 3

Stimuli-responsive nanoparticles in cancer chemotherapy. The emergence of stimuli-sensitive nanocarriers has revolutionized cancer therapy, since there are specific features in the tumor microenvironment including low pH levels and redox imbalance. The increase in GSH levels and decrease in pH levels can cause release of OXA from nanoparticles in cancer therapy.

Fig. 4

Ligand-modified nanoparticles and exosomes in OXA delivery. The functionalization of nanoparticles with ligands has been emerged as a promising strategy in cancer therapy. The unmodified nanoparticles improve the pharmacokinetic profile of OXA, but ligand-functionalized nanoparticles can specifically target the tumor cells due to overexpression of receptors. Moreover, functionalization can increase the internalization of nanoparticles in the tumor cells through endocytosis. The exosomes are also ideal carriers for OXA, since their biocompatibility is high and they can delivery cargo with high efficacy.