Supramolecular Theranostic Nanomedicine for In Situ Self-Boosting Cancer Photochemotherapy

Abstract

Although traditional nanomedicines have enhanced the therapeutic efficacy and improved the survival quality of cancer patients, random drug release and drug resistance are deep-rooted problems hindering their clinical application. A precise nanoplatform combing chemotherapy and photodynamic therapy (PDT) is developing as a new therapeutic strategy to overcome the above challenges. Herein, a novel supramolecular nanomedicine is ingeniously constructed for in situ selfboosting cancer photochemotherapy. Hydrophilic polyethylene glycol (PEG) chains or β-cyclodextrin (β-CD) hosts are first conjugated onto tetraphenyl porphyrin (TCPP) to improve the solubility of TCPP and decrease their π−π stacking interactions, guaranteeing a high-efficiency PDT. Then, two camptothecin (CPT) molecules are linked together via a reactive oxygen species (ROS)-responsive thioketal bond, which averts the premature burst release of CPT and realizes in situ drug release at the tumor site where PDT is performed, resulting in an enhanced chemotherapy. Benefiting from the collaboration of host−guest complexation between β-CD and CPT, multiple intermolecular hydrogen bonds of β-CD, π−π stacking interactions among CPT and TCPP as well as PEG shell protection, a prolonged blood circulation time, and a selective tumor accumulation are acquired, which facilitate the synergistic photochemotherapy and bring a pre-eminent antitumor response with a low systemic toxicity.

Unleashing the Power of PET-RAFT Polymerization: Journey from Porphyrin-Based Photocatalysts to Combinatorial Technologies and Advanced Bioapplications

“…The combination of aromatic macrocyclic compounds and CLRP has led to innovative developments in the design of biomacromolecules for disease treatment. , Aromatic macrocyclic compounds are well-known for their multifaceted biocompatibility and remarkable biological activities, making them suitable for use in polymeric drug systems and synergistic treatment. ,, Studies have shown promising results regarding the efficacy of these biomacromolecules in treating various diseases such as cancer, , cardiovascular disorders, and wound healing . The PET-RAFT process, which utilizes catalysts derived from aromatic macrocyclic compounds, has significantly advanced the field, enabling the development of novel designs and applications.…”

Smart organic materials based on macrocycle hosts

“…[64][65][66] In addition to targeted delivery, these supramolecular vesicles can also effectively boost and manipulate the generation of singlet oxygen species (ROS) for antibacterial applications when photosensitizers, such as porphyrins and particular types of AIEgens, are incorporated into the vesicular structures. [67][68][69] Therefore, the modification of photosensitizers onto macrocycles or the encapsulation of guest molecules with ROS productivity by macrocycles is broadly performed to afford supramolecular nanocarriers with controllable photosensitizing ability, 70 whereby the loading and controlled release of antibiotics are also accessible in the meantime. 71…”

Advancement of regulating cellular signaling pathways in NSCLC target therapy via nanodrug

“…Similarly, it has significant implications for the regulation of drug resistance ( Vincent et al, 2022 ). Based on the anatomical and pathophysiological differences between normal and tumor cells, the NPs have strong enhanced permeability and retention (EPR) effect, as shown in Figure 2 ( Ikeda-Imafuku et al, 2022 ; Wu et al, 2023 ). Nanocarriers can be divided into natural polymer and synthetic polymer materials, most of which have excellent biocompatibility, stability, safety, non-toxicity and modifiability, mainly including virus-like particles, poly lactic glycolic acid (PLGA), liposomes, dendrimers, metal organic framework compounds, as shown in Figure 3 ( Guo and Jiang, 2020 ; Ji et al, 2023 ).…”