<p>Folate-mediated and pH-responsive chidamide-bound micelles encapsulating photosensitizers for tumor-targeting photodynamic therapy</p>

Abstract

Background: Nonspecific tumor targeting, potential relapse and metastasis of tumor after treatment are the main barriers in clinical photodynamic therapy (PDT) for cancer, hence, inhibiting relapse and metastasis of tumor is significant issues in clinic. Purpose: In this work, chidamide as a histone deacetylases inhibitor (HADCi) was bound onto a pH-responsive block polymer folate polyethylene glycol- b -poly(aspartic acid) (PEG- b -PAsp) grafted folate (FA-PEG- b -PAsp) to obtain the block polymer folate polyethylene glycol- b -poly(asparaginyl-chidamide) (FA-PEG- b -PAsp-chidamide, FPPC) as multimodal tumor-targeting drug-delivery carrier to inhibiting tumor cell proliferation and tumor metastasis in mice. Methods: Model photosensitizer pyropheophorbide- a (Pha) was encapsulated by FPPC in PBS to form the polymer micelles Pha@FPPC [folate polyethylene glycol- b -poly(asparaginyl-chidamide) micelles encapsulating Pha]. Pha@FPPC was characterized by transmission electron microscope and dynamic light scattering; also, antitumor activity in vivo and in vitro were investigated by determination of cellular ROS level, detection of cell apoptosis and cell cycle arrest, PDT antitumor activity in vivo and histological analysis. Results: With favorable and stable sphere morphology under transmission electron microscope (TEM) (~93.0 nm), Pha@FPPC greatly enhanced the cellular uptake due to its folate-mediated effective endocytosis by mouse melanoma B16-F10 cells and the yield of ROS in tumor cells induced by PDT, and mainly caused necrocytosis and blocked cell growth cycle not only in G2 phase but also in G1/G0 phase after PDT. Pha@FPPC exhibited lower dark cytotoxicity in vitro and a better therapeutic index because of its higher dark cytotoxicity/photocytotoxicity ratio. Moreover, Pha@FPPC not only significantly inhibited the growth of implanted tumor and prolonged the survival time of melanoma-bearing mice due to both its folate-mediated tumor-targeting and selectively accumulation at tumor site by EPR (enhanced permeability and retention)effect as micelle nanoparticles but also remarkably prevented pulmonary metastasis of mice melanoma after PDT compared to free Pha, demonstrating its dual antitumor characteristics of PDT and HDACi. Conclusion: As a folate-mediated and acid-activated chidamide-grafted drug-delivery carrier, FPPC may have great potential to inhibit tumor metastasis in clinical photodynamic treatment for cancer because of its effective and multimodal tumor-targeting performance as photosensitizer vehicle.

pH-Responsive Polymer Nanomaterials for Tumor Therapy

“…To overcome the shortcomings of the non-specific tumor therapy associated with PDT, Li et al ( 179 ) and He et al ( 180 ) applied nanomaterials with stimulus-response to PDT, which made the therapeutic drugs release specifically at the tumor site, reducing the non-specific phototoxicity of PDT and improving the anti-tumor effect. Ma et al ( 181 ) combined chidamide as a histone deacetylase inhibitor (HADCi) with pH-responsive block polymer folate PEG-b-poly(aspartic acid) (PEG-b-PAsp)-grafted folate (FA-PEG-b-PAsp) to obtain block polymer folate PEG-b-poly(asparaginyl-chidamide) [FA-PEG-b-PAsp-chidamide (FPPC)]. Then the model photosensitizer pyropheophorbide a (Pha) was coated with FPPC and polymer micelles (Pha@FPPC) were formed in PBS.…”

<p>Combination Treatment of Cervical Cancer Using Folate-Decorated, pH-Sensitive, Carboplatin and Paclitaxel Co-Loaded Lipid-Polymer Hybrid Nanoparticles</p>

“…17 So FA decorated nanoparticle formulations were developed for targeted cancer therapy. [18][19][20] The present research focuses on the development of folate-decorated, pH-sensitive LPNs. Loading carboplatin (CBP) and paclitaxel (PTX), LPNs were expected to combine the therapeutic effects of CBP and PTX, thus show synergistic ability on cervical cancer.…”

Chidamide stacked in magnetic polypyrrole nano-composites counter thermotolerance and metastasis for visualized cancer photothermal therapy

“…CDM was obtained according to our previous synthesis method (Ma et al., 2019 ). MPP (50 mg) was dispersed in tetrahydrofuran (THF) followed by the addition of CDM (10 mg) solution.…”