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

Abstract

Photothermal therapy (PTT) has become one of the most promising therapies in cancer treatment as its noninvasiveness, high selectivity, and favorable compliance in clinic. However, tumor thermotolerance and distal metastasis reduce its efficacy, becoming the bottleneck of applying PTT in clinic. In this study, a chidamide-loaded magnetic polypyrrole nanocomposite (CMPP) has been fabricated as a visualized cancer photothermal agent (PTA) to counter tumor thermotolerance and metastasis. The efficacy of CMPP was characterized by in vitro and in vivo assays. As a result, this kind of magnetic polypyrrole nanocomposites were black spherical nanoparticles, possessing a favorable photothermal effect and the suitable particle size of 176.97 ± 1.45 nm with a chidamide loading rate of 12.92 ± 0.45%. Besides, comparing with PTT, CMPP exhibited significantly higher cytotoxicity and cellular apoptosis rate in two tumor cell lines (B16-F10 and HepG2). In vivo study, the mice showed obvious near-infrared (NIR) and magnetic resonance imaging (MRI) dual-modal imaging at tumor sites and sentinel lymph nodes (SLNs); on the other hand, magnetic targeting guided CMPP achieved a cure level on melanoma-bearing mice through preventing metastasis and thermotolerance. Overall, with high loading efficiency of chidamide and strong magnetic targeting to tumor sites and SLNs, CMPP could significantly raise efficiency of PTT by targeting tumor thermotolerance and metastasis, and this strategy may be exploited therapeutically to upgrade PTT with MPP as one of appropriate carriers for histone deacetylase inhibitors (HDACis).

Antitumor Applications of Photothermal Agents and Photothermal Synergistic Therapies

“…So far, organic PTAs based on NIR response small molecules (anthocyanin, porphyrin [ 101 ], phthalocyanine [ 102 ], and theobromine [ 103 ]) and semiconductor polymer nanoparticles (polyaniline [ 104 ] and polypyrrole [ 105 ]) have shown excellent therapeutic efficacy and have been widely studied as potential PTAs.…”

“…So far, organic PTAs based on NIR response small molecules (anthocyanin, porphyrin [101], phthalocyanine [102], and theobromine [103]) and semiconductor polymer nanoparticles (polyaniline [104] and polypyrrole [105]) have shown excellent therapeutic ef- (B) fluorescence images of HeLa cells cultured with BP@PEG/Ce6 NSs; (C) intracellular ROS generation of HeLa cells treated with BP@PEG/Ce6 NSs and irradiated with 660 nm laser. Relative viabilities of HeLa cells after being treated with BP@PEG NSs, Ce6, and BP@PEG/Ce6 NSs at different concentrations of BP@PEG NSs (1, 2.5, 5, 10, 25, and 50 ppm) or Ce6 (0.13, 0.325, 0.65, 1.3, 3.25, and 6.5 ppm); (D) without and (E) with irradiation (660 nm, 0.65 W•cm −2 , 10 min); (F) fluorescence images of HeLa cells co-stained with Calcein AM (live cells, green) and PI (dead cells, red) upon the addition of BP@PEG NSs, Ce6, and BP@PEG/Ce6 NSs without and with irradiation (660 nm, 0.65 W•cm −2 , 10 min).…”

Advances in the Application of Nanomaterials to the Treatment of Melanoma

“…A chidamide-loaded magnetic polypyrrole nanocomposite was designed as a visualized photothermal cancer chemotherapy to combat tumor heat resistance and metastasis. It showed sound anticancer effects in in vivo and in vitro melanoma experiments and inhibited melanoma metastasis in mice [ 173 ].…”