Linear Chimeric Triblock Molecules Self‐Assembled Micelles with Controllably Transformable Property to Enhance Tumor Retention for Chemo‐Photodynamic Therapy of Breast Cancer

Abstract

Although nanoparticles are expected to revolutionize cancer treatment, their low efficacy remains the greatest limiting factor. Recent investigations found that nanoparticles' golden principle, the enhanced permeability and retention (EPR) effect, is limited by the complicated tumor microenvironment. Herein, novel transformable nanomaterials are designed to utilize the EPR effect more effectively. By tandem conjugation of the hydrophobic head (chlorin e6 (Ce6) or bilirubin (BR)), peptide to form hydrogen bond (Phe-Phe-Val-Leu-Lys (FFVLK)), and hydrophilic tail (polyethylene glycol (PEG)), chimeric molecules that can form micelles (Ce6/BR-FFVLK-PEG) in aqueous solution are synthesized. Notably, the spherical micelles retain shape transformability. After circulation and distribution, they respond to 650 nm laser irradiation, and morphologically change into nanofibers so as to facilitate their retention markedly inside the tumor. Upon loading a reactive oxygen species-responsive paclitaxel dimer with thioketal linker (PTX 2 -TK), the resultant PTX 2 -TK@Ce6/BR-FFVLK-PEG nanomedicine serves as a potent chemo-photodynamic therapeutic for cancer treatment. Evaluations at both cell level and animal level reveal that PTX 2 -TK@Ce6/BR-FFVLK-PEG exhibits superior biocompatibility and biodistribution, and suppresses 82.6% of in vitro cell growth and 61.8% of in vivo tumor growth at a common dose of intravenous injection (10 mg kg −1 PTX and 3.3 mg kg −1 Ce6), becoming a novel nanomedicine with extraordinary potential in cancer therapy.

Polymeric Nanoparticles with ROS‐Responsive Prodrug and Platinum Nanozyme for Enhanced Chemophotodynamic Therapy of Colon Cancer

“…[ 1 ] However, the use of chemotherapeutics, such as irinotecan and topotecan derivatives, which are camptothecin (CPT) analogs, is disadvantageous because of uncontrolled release behavior and poor targeting ability, which easily induce systemic toxicity, immunosuppression, and drug resistance. [ 2 ] To date, numerous studies have confirmed that combined therapy holds promising prospects in cancer treatment. [ 3 ] Notably, photodynamic therapy (PDT), a non‐invasive method for cancer therapy, can generate reactive oxygen radicals (ROS) under light irradiation, which causes irreversible damage to tumor cells.…”

GSH-responsive SN38 dimer-loaded shape-transformable nanoparticles with iRGD for enhancing chemo-photodynamic therapy

“…Recently, transformable linear chimeric triblock molecules Ce6/BR-FFVLK-PEG were designed by our lab 18 . The hydrophobic head [chlorin e6 (Ce6) or bilirubin (BR)], and hydrophilic tail [polyethylene glycol (PEG)] were tandem conjugated with Phe-Phe-Val-Leu-Lys (FFVLK) for forming spherical micelles.…”

Size Dependency of Circulation and Biodistribution of Biomimetic Nanoparticles: Red Blood Cell Membrane-Coated Nanoparticles

“…For conventional nanoparticles, their circulation time, cellular uptake, and in vivo tissue distribution are mainly controlled by various factors, such as diameter, shape, surface charge, and rigidness [1,33,34]. For instance, micro-sized, long, flexible filomicelles could not be internalized by macrophages and have a very long circulation of days or even weeks [35].…”