Nanomedicine tactics in cancer treatment: Challenge and hope

Cabozantinib-Loaded PLGA Nanoparticles: A Potential Adjuvant Strategy for Surgically Resected High-Risk Non-Metastatic Renal Cell Carcinoma

“…To deal with the main hurdle in the practical application of multi-TKIs, including severe dose-related adverse events owing to particular effects on normal organs, hydrophobicity, and low oral bioavailability in addition to drug resistance, nanoparticles (NPs) based on multi-TKIs have attracted ever-increasing attention in recent years [ 48 ]. The enhanced permeability retention (EPR) effect allows for the passive targeting by NPs (ranging from 40 to 400 nm in size) when administrated intravenously due to vascular leakage and defective lymphatic drainage in solid tumors, enabling long-term circulation with increased efficacy and reduced toxicity by decreasing drug accumulation in normal organs [ 48 , 49 , 50 , 51 , 52 , 53 ]. More importantly, NPs can significantly improve the aqueous solubility and, eventually, the oral bioavailability of poorly soluble drugs due to a smaller size, greater surface area to volume ratio, and higher cell penetration ability [ 48 , 54 , 55 ].…”

“…More importantly, NPs can significantly improve the aqueous solubility and, eventually, the oral bioavailability of poorly soluble drugs due to a smaller size, greater surface area to volume ratio, and higher cell penetration ability [ 48 , 54 , 55 ]. Currently, several efforts to design systematic formulations to overcome the poor solubility of hydrophobic TKIs have demonstrated that different polymeric nanocomplex NPs significantly improve the anti-cancer efficacy of TKIs, such as sorafenib, ponatinib, and nilotinib, by enhancing their bioavailability and allowing for the efficient delivery of the drug to tumor tissues while reducing adverse side effects [ 48 , 49 , 50 , 51 , 52 , 53 , 56 , 57 , 58 , 59 , 60 , 61 ].…”

“…We therefore hypothesized that translating the multi-TKIs CZ into NP formulations is an ideal strategy as it may increase drug accumulation in tumor cells via the EPR effect and reduce side effects. Poly(lactic-co-glycolic acid) (PLGA), which is a polymer currently approved for clinical usage, hydrolyzes into its monomers (lactic and glycolic acid) and then metabolizes in vivo to be easily excreted from the body [ 48 , 49 , 50 , 51 , 52 , 58 , 59 , 60 , 61 ]. Therefore, it has been safely used to prepare intravenously injectable NP formulations [ 48 , 49 , 50 , 51 , 52 , 58 , 59 , 60 , 61 ].…”

“…Poly(lactic-co-glycolic acid) (PLGA), which is a polymer currently approved for clinical usage, hydrolyzes into its monomers (lactic and glycolic acid) and then metabolizes in vivo to be easily excreted from the body [ 48 , 49 , 50 , 51 , 52 , 58 , 59 , 60 , 61 ]. Therefore, it has been safely used to prepare intravenously injectable NP formulations [ 48 , 49 , 50 , 51 , 52 , 58 , 59 , 60 , 61 ]. In addition to their biodegradable properties, PLGA synthetic NPs are the most extensively studied of all commercially available polymeric NPs for the delivery of anti-cancer drugs due to their non-immunogenicity, microcytotoxicity, biocompatibility, high drug loading capacity, and controlled slow-release profiles [ 48 , 49 , 50 , 51 , 52 , 58 , 59 , 60 , 61 ].…”

“…Therefore, it has been safely used to prepare intravenously injectable NP formulations [ 48 , 49 , 50 , 51 , 52 , 58 , 59 , 60 , 61 ]. In addition to their biodegradable properties, PLGA synthetic NPs are the most extensively studied of all commercially available polymeric NPs for the delivery of anti-cancer drugs due to their non-immunogenicity, microcytotoxicity, biocompatibility, high drug loading capacity, and controlled slow-release profiles [ 48 , 49 , 50 , 51 , 52 , 58 , 59 , 60 , 61 ]. This study explored the feasibility and the anti-metastatic efficacy of CZ-loaded PLGA NPs (CZ-PLGA-NPs) as the clinical adjuvant routine following a nephrectomy for high-risk non-metastatic RCC for preventing or reducing post-nephrectomy metastatic relapse.…”