Carrier-Enhanced Anticancer Efficacy of Sunitinib-Loaded Green Tea-Based Micellar Nanocomplex beyond Tumor-Targeted Delivery

Abstract

Although a few nanomedicines have been approved for clinical use in cancer treatment, that recognizes improved patient safety through targeted delivery, their improved efficacy over conventional drugs has remained marginal. One of the typical drawbacks of nanocarriers for cancer therapy is a low drug-loading capacity that leads to insufficient efficacy and requires an increase in dosage and/or frequency of administration, which in turn increases carrier toxicity. In contrast, elevating drug-loading would cause the risk of nanocarrier instability, resulting in low efficacy and off-target toxicity. This intractable drug-to-carrier ratio has imposed constraints on the design and development of nanocarriers. However, if the nanocarrier has intrinsic therapeutic effects, the efficacy would be synergistically augmented with less concern for the drug-to-carrier ratio. Sunitinib-loaded micellar nanocomplex (SU-MNC) was formed using poly(ethylene glycol)-conjugated epigallocatechin-3-O-gallate (PEG-EGCG) as such a carrier. SU-MNC specifically inhibited the vascular endothelial growth factor-induced proliferation of endothelial cells, exhibiting minimal cytotoxicity to normal renal cells. SU-MNC showed enhanced anticancer effects and less toxicity than SU administered orally/intravenously on human renal cell carcinoma-xenografted mice, demonstrating more efficient effects on anti-angiogenesis, apoptosis induction, and proliferation inhibition against tumors. In comparison, a conventional nanocarrier, SU-loaded polymeric micelle (SU-PM) comprised of PEG-b-poly(lactic acid) (PEG-PLA) copolymer, only reduced toxicity with no elevated efficacy, despite comparable drug-loading and tumortargeting efficiency to SU-MNC. Improved efficacy of SU-MNC was ascribed to the carrier−drug synergies with the highperformance carrier of PEG-EGCG besides tumor-targeted delivery.

Polyphenol‐Containing Nanoparticles: Synthesis, Properties, and Therapeutic Delivery

“…In another study, sunitinib (SU), a tyrosine kinase inhibitor, was encapsulated in the EGCG‐based nanocarrier (MNC) for cancer treatment. [ 141 ] The SU‐loaded MNCs were prepared by PEG‐EGCG and SU. Carrier‐enhanced targeting efficacy was systematically analyzed in comparison with a conventional nanocarrier PEG‐ b ‐poly(lactic acid) (PEG‐PLA) MNC.…”

Unraveling the gallol-driven assembly mechanism of thermoreversible supramolecular hydrogels inspired by ascidians

“…18 Although the exact mechanism underlying these intrinsic features remains unclear, it is mainly associated with reversible H-bonding interactions between pyrogallol groups from TOPA together with metal-pyrogallol coordination, and pyrogallol-mediated oxidative covalent crosslinking. 19,20 Recently, pyrogallol-containing polyphenols, such as tannic acid (TA), [21][22][23] epigallocatechin, 24,25 and epigallocatechin gallate, 26,27 among others, have gained great attention as building blocks for designing functional biomaterials. In particular, the multi-binding and metal ion coordination abilities of TA have been extensively exploited for the construction of supramolecular hydrogels with adhesive or shape memory behavior.…”

Phytofabrication of Nanoparticles as Novel Drugs for Anticancer Applications

“…Recently, one study reported that self-assembly of the PEG–EGCG with Sunitinib (SU) leads to the formation of stable micellar nanocomplex (SU-MNC), which have greater anticancer effectiveness than conventional SU formulations on human renal cell carcinoma-xenografted mice [87]. When injected into mice, SU-MNC efficiently inhibited tumor growth with less systemic toxicity.…”