TY - JOUR
T1 - A photo-triggered antifungal nanoplatform with efflux pump and heat shock protein reversal activity for enhanced chemo-photothermal synergistic therapy
AU - Yang, Dongliang
AU - Tu, Yuexing
AU - Wang, Xiaorui
AU - Cao, Changyu
AU - Hu, Yanling
AU - Shao, Jinjun
AU - Weng, Lixing
AU - Mou, Xiaozhou
AU - Dong, Xiaochen
N1 - Publisher Copyright:
© 2021 The Royal Society of Chemistry.
PY - 2021/5/7
Y1 - 2021/5/7
N2 - Drug-resistant pathogens are less sensitive to traditional antibiotics in many stubborn infections. It is imminently desirable to have an effective alternative therapeutic agent for combating drug-resistant pathogen infections. Herein, a photo-triggered multifunctional nanoplatform (TMOB/FLU@PCM NPs) with efflux pump and heat shock protein expression reversal activity is developed for the highly effective eradication of drug-resistant fungi. Upon 808 nm laser excitation, the hyperthermia originating from a BODIPY derivative (TMOB) can not only melt the phase-change material (PCM) vehicle consisting of hexadecanol and cis-2-dodecenoic acid (BDSF) to on-demand release the quorum sensing molecule BDSF and the antifungal drug fluconazole (FLU), but can also destroy the integrity of the C. albicans cell membrane. Thanks to the release of BDSF from TMOB/FLU@PCM NPs, the expression of drug efflux pumps (MDR1, CDR2, CDR4) and thermotolerant proteins (HSP12, HSP21, HSP60, HSP90) is inhibited, which further boosts the therapeutic effect of chemo/photothermal therapy. Moreover, the hyphal and biofilm formation of C. albicans can be blocked by TMOB/FLU@PCM NPs under 808 nm laser irradiation. In vitro and in vivo results indicate that TMOB/FLU@PCM NPs with good biosafety can efficiently eliminate clinical azole-resistant C. albicans. Thus, TMOB/FLU@PCM NPs exhibits a promising future in the treatment of azole-resistant C. albicans infection.
AB - Drug-resistant pathogens are less sensitive to traditional antibiotics in many stubborn infections. It is imminently desirable to have an effective alternative therapeutic agent for combating drug-resistant pathogen infections. Herein, a photo-triggered multifunctional nanoplatform (TMOB/FLU@PCM NPs) with efflux pump and heat shock protein expression reversal activity is developed for the highly effective eradication of drug-resistant fungi. Upon 808 nm laser excitation, the hyperthermia originating from a BODIPY derivative (TMOB) can not only melt the phase-change material (PCM) vehicle consisting of hexadecanol and cis-2-dodecenoic acid (BDSF) to on-demand release the quorum sensing molecule BDSF and the antifungal drug fluconazole (FLU), but can also destroy the integrity of the C. albicans cell membrane. Thanks to the release of BDSF from TMOB/FLU@PCM NPs, the expression of drug efflux pumps (MDR1, CDR2, CDR4) and thermotolerant proteins (HSP12, HSP21, HSP60, HSP90) is inhibited, which further boosts the therapeutic effect of chemo/photothermal therapy. Moreover, the hyphal and biofilm formation of C. albicans can be blocked by TMOB/FLU@PCM NPs under 808 nm laser irradiation. In vitro and in vivo results indicate that TMOB/FLU@PCM NPs with good biosafety can efficiently eliminate clinical azole-resistant C. albicans. Thus, TMOB/FLU@PCM NPs exhibits a promising future in the treatment of azole-resistant C. albicans infection.
UR - http://www.scopus.com/inward/record.url?scp=85105461321&partnerID=8YFLogxK
U2 - 10.1039/d1bm00457c
DO - 10.1039/d1bm00457c
M3 - 文章
C2 - 33861264
AN - SCOPUS:85105461321
SN - 2047-4830
VL - 9
SP - 3293
EP - 3299
JO - Biomaterials Science
JF - Biomaterials Science
IS - 9
ER -