Rationally Driven Drug Nonradiative Decay via a Label‐Free Polyprodrug Strategy to Renew Tumor Cascade Photothermal‐Chemotherapy

Abstract

Drugs are frequently used for only chemotherapy that ignores their photophysical properties that potentially endow them with other therapeutic potency. Additionally, current photothermal‐chemotherapy replies on the codelivery of drugs and photothermal agents, but their spatiotemporal delivery and precise release is unsatisfactory. Herein, label‐free doxorubicin (DOX) polyprodrug nanoparticles (DPNs) are formulated from disulfide bonds‐tethered DOX polyprodrug amphiphiles (PDMA‐b‐PDOXM). Benefiting from boosted nonradiative decay of high‐density DOX, significant fluorescence quenching and photothermal effects are observed for DPNs without common photothermal agents. Upon cellular uptake and laser irradiation, the heat can promote lysosomal escape of DPNs into reductive cytosol, whereupon free DOX is released to activate chemotherapy and fluorescence, achieving rational cascade photothermal‐chemotherapy. The current label‐free polyprodrug strategy can make full use of drugs; it provides an alternative insight to extend the therapeutic domain of drugs.

Nanocarriers for intracellular co-delivery of proteins and small-molecule drugs for cancer therapy

“…Photodynamic therapy (PDT) has gradually become a new type of tumor therapy because of its low invasiveness, high cure rate, and little damage to the body, which has attracted great attention in preclinical research and clinical practice ( Lucky et al, 2015 ; Zhang Y et al, 2018 ; Miao et al, 2019 ; Zhong et al, 2021 ; Zhang et al, 2022 ). In recent years, more and more tumor therapy systems combined with protein therapy and photodynamic therapy have emerged and achieved promising results.…”

Intra- and Intermolecular Synergistic Engineering of Aggregation-Induced Emission Luminogens to Boost Three-Photon Absorption for Through-Skull Brain Imaging

“…30 The fluorophores with these features are prone to show an aggregation-caused quenching (ACQ) effect, leading to decreased or quenched emission in the aggregated state. 34,35 To overcome this ACQ effect, various fluorophores displaying aggregation-induced emission (AIE) features were developed for bioimaging and theranostics thanks to their bright emission and good photostability in the aggregate state. 36−39 A number of AIE luminogens (AIEgens) reported for 3PFM bioimaging are based on a tetraphenylethylene-or phenyl-bridged structure, which always display moderate three-photon absorption activity owing to their less effective conjugated structures.…”

“…This result suggests that introducing an electron-donor (D) and -acceptor (A) and expanding the conjugation length of molecule may result in better charge separation to enhance the 3PA cross section . The fluorophores with these features are prone to show an aggregation-caused quenching (ACQ) effect, leading to decreased or quenched emission in the aggregated state. , To overcome this ACQ effect, various fluorophores displaying aggregation-induced emission (AIE) features were developed for bioimaging and theranostics thanks to their bright emission and good photostability in the aggregate state. − A number of AIE luminogens (AIEgens) reported for 3PFM bioimaging are based on a tetraphenylethylene- or phenyl-bridged structure, which always display moderate three-photon absorption activity owing to their less effective conjugated structures. ,,, Besides molecular design, the previous studies reveal that the intermolecular interactions among molecules in the aggregate state could also facilitate the nonlinear optical activity of materials. − Recently, the intermolecular charge-transfer interactions were demonstrated to improve 2PA of organic cocrystals . Thus, another possible way to improve the 3PA property of materials is to exploit excitonic coupling and intermolecular interactions among the aggregated molecules.…”

New Water-Soluble Magnetic Field-Induced Drug Delivery System Obtained Via Preferential Molecular Marriage over Narcissistic Self-Sorting

“…Capping ligands in metal nanoparticles (MNPs) are indispensable due to their role in stabilizing and maintaining the structural and physical properties (size, shape, and morphology) of MNPs. , Polymer-capped MNPs have been investigated for decades for a variety of applications, including sensing, , drug delivery, − photodynamic therapy, antimicrobials, contrast agents for magnetic resonance imaging, catalysis, and molecular electronics . Among these, drug delivery has drawn the most attention due to its additional therapeutic properties when combined with chemotherapy, for instance, hyperthermia − and radiation therapy, , using polymer functionalization on iron oxide and gold NPs, have been studied.…”

“…Even with a dynamic exchange, they were able to recognize the same types for an amphiphilic random copolymer containing hydrophilic poly­(ethylene glycol) (PEG) and hydrophobic alkyl pendants in aqueous media. A number of groups have investigated the delivery of hydrophobic drugs using self-assembled polymeric nano-micelles (e.g., amphiphilic PEG–PLA micelles encapsulating doxorubicin (DOX) and paclitaxel drugs ,,,,,,, and PEGylated phospholipid-based block copolymers for the encapsulation of paclitaxel, diazepam, and vasoactive intestinal peptide , ) in an aqueous environment for site-specific drug delivery. They discussed the role that hydrophobic interactions play in drug–PLA interactions.…”