NIR‐II Absorbing Semiconducting Polymer‐Triggered Gene‐Directed Enzyme Prodrug Therapy for Cancer Treatment

Abstract

Exploration of facile strategies for precise regulation of target gene expression remains highly challenging in the development of gene therapies. Especially, a stimuli‐responsive nanocarrier integrated with ability of noninvasive remote control for treating wide types of cancers is rarely developed. Herein, a NIR‐II absorbing semiconducting polymer (PBDTQ) is employed to remotely activate the heat‐inducible heat‐shock protein 70 (HSP70) promoter under laser irradiation, further realizing regulation of gene‐directed enzyme prodrug therapy (GDEPT) for cancer treatment in mild hyperthermia. In this multifunctional nanocomposite, the PBDTQ and double suicide gene plasmid (pSG) based on HSP70 promoter are incorporated into a lipid complex. Upon NIR‐II laser excitation, the mild photothermal effect (≈43 °C) generated from PBDTQ can cause the release of pSG and activation of HSP70 promoter, and then upregulate suicide gene expression triggered by the HSP70 promoter which can further convert the nontoxic prodrug into its cytotoxic metabolites. Therefore, this work demonstrates a universal NIR‐II laser‐triggered GDEPT using semiconducting polymers as the photothermal generator for cancer treatment with minimized collateral damage and nontargeted side effects.

Simultaneous Enhancement of the Long-Wavelength NIR-II Brightness and Photothermal Performance of Semiconducting Polymer Nanoparticles

“…Specifically, the mass extinction coefficients (ε) of PBQ3–45 NPs at 1064 nm (the detailed calculation method is presented in Figure S5) were 7.2, 12.6, 20.3, 28.5, and 27.5 L/(g cm), respectively. Compared with the previously reported semiconducting polymer nanoparticles with similar chemical structures, − PBQ45 NPs not only exhibited a red-shifted absorption spectrum but also possessed larger mass extinction coefficients. This indicates that the repeating unit number of the semiconducting polymers plays an important role in their band gap and mass extinction coefficients.…”

“…PBQx were prepared using the Stille polymerization from (4,8-bis­((2-octyldodecyl)­oxy)­benzo­[1,2,b:4,5- b ′]­dithiophene-2,6-diyl)­bis­(trimethylstannane) and 4,9-dibromo-6,7-bis­(4-(hexyloxy)­phenyl)-[1,2,5]-thiadiazole­[3,4- g ]­quinoxaline according to the procedure we reported earlier. , The reaction progress was monitored by the UV–vis–NIR spectrum. The reaction times were set to 3, 6, 13, and 15 min as well as 2 h, respectively.…”

Conjugated polymers for biomedical applications

“…Therefore, it is an effective strategy based on photothermal materials to regulate gene expression for influencing the cellular environment. 109,110 Wang's group designed the maleimide group functionalized poly[2,6 0 -4,8-di(5-ethylhexylthienyl)benzo[1,2-b;3,4-b]dithiophene-alt-5-dibutyloctyl-3,6-bis(5bromothiophen-2-yl)pyrrolo [3,4-c]pyrrole-1,4dione] (PDPPDBT) nanoparticles modified with cell-penetrating peptides (CPNs-Tat). 111 Under NIR light, CPNs-Tat could convert light into heat, triggering heat-inducible heat shock protein (HSP-70) promoter and inducing downstream gene expression.…”

Conjugated Polymers for Gene Delivery and Photothermal Gene Expression

“…d) Gene delivery and NIR light‐activated tumor therapy for GDEPT/PTT. Reproduced with permission [90] . Copyright 2021, Wiley‐VCH.…”