Investigation Of NIR-controlled Smart Drug Delivery System For Cancer Theranostics

Multimodal imaging-guided synergistic therapy has attracted widely interest for the excellent accurate diagnosis and therapeutic efficiency.Developing a new theranostic nanomedicine platform for imaging-guided,visualized synergistic photothemal therapy（PTT）and photodynamic therapy（PDT）for cancer is currently a promising way to achieve the precise cancer therapy.With the development of nanotechnology,smart nanocarriers which possess the capacity to combine multiple modalities for the diagnosis or treatment on one probe,have been receiving tremendous attention and have now become an important field in medical research.Herein,indocyanine green（ICG）and tetradecanol（TD）co-loaded CuS@mSiO₂temperature sensitive nanostructure,as well as ICG loaded BSA-bioinspired adolinium hybrid-functionalized hollow gold nanoshells（Au@BSA-Gd）were developed for multimodal imaging guided PTT/PDT cancer therapy.We systematically studied the theranostic nanocarriers of the morphological structure,particle size,potential,drug loading efficiency,release behaviors,multimodal imaging studies,combined PTT/PDT treatment in vitro and in vivo,and the bio-safety evaluation.The combination of precise imaging detection and synergistic PTT/PDT effect provides a new idea to improve the bioavailability and efficiency of cancer therapy.1.TD-controlled and ICG-loaded CuS@mSiO₂ for fluorescence/PA dual-imaging guided combined PTT/PDT cancer therapyIn this work,we report a novel 1-tetradecanol（TD）-controlled and indocyanine green（ICG）-loaded CuS@mSiO₂ phototherapy nanoplatform（CuS@mSiO₂-TD/ICG）.The CuS@mSiO₂ nanoparticles prepared by a facile one-pot approach can serve as drug-delivery vehicles to transport the NIR absorbing phototherapeutic agent（ICG）within the mesoporous cavities.Meanwhile a phase-change molecule（PCM）,TD,is introduced as a thermo-sensitive gatekeeper to avoid the premature release of loaded ICG.Noticeably,the combined therapy is irradiated at an 808 nm single-light wavelength,thus performing the photothermal therapy（PTT）based on CuS@mSiO₂nanoparticles as well as simultaneous photodynamic（PDT）/PTT effect based on ICG.Furthermore,ICG also has the function of dual in vivo fluorescence imaging and photoacoustic（PA）imaging.Thus,this nanoplatform holds the characteristics of gatekeeper-controlled release behavior,dual model imaging and single-light triggered PTT/PDT treatment,which can be a promise for future cancer therapy due to their markedly improved therapeutic efficacy and decreased systemic toxicity.We first tested the characterizations of morphology,size,zeta potential,pore size,drug loading,temperature controlled drug release behaviours,in vitro PTT and PDT effect.After that,we also evaluated the cellular uptake,cytotoxicities,cellular ROS detection,fluorescence/PA dual imaging in vivo and synergistic PTT/PDT antitumor efficiency in vivo.The in vitro characterizations confirmed the successful preparation of CuS@mSiO₂-TD/ICG nanoparticles.What?s more,the cellular and in vivo animal studies suggested the nanoplatform could perform combined PTT/PDT cancer treatment without obvious systemic toxicity.2.BSA-bioinspired gadolinium hybrid-functionalized hollow gold nanoshells for fluorescence/PA/CT/MR quadmodal imaging guided PTT/PDT cancer therapy:In this research,we constructed an innovative multifunctional drug delivery platform by gadolinium（Gd）-based bovine serum albumin（BSA）hybrid-coated hollow gold nanoshells（Au@BSA-Gd）.The obtained nanoparticles exhibited excellent photothermal effect and PA/CT activity.Besides,the BSA-bioinspired gadolinium complex endowed the nanoparticles with an excellent T₁ contrast agent for magnetic resonance imaging（MRI）.In addition,the near-infrared（NIR）absorbing phototherapeutic agent[indocyanine green（ICG）]was loaded into to perform photodynamic/photothermal property and near-infrared fluorescence/PA imaging capability.As a result,the well-designed nanocomposites（ICG-Au@BSA-Gd）endow simultaneousphotodynamic/photothermalcombinedcancertherapyand fluorescence/PA/CT/MR quadmodal imaging abilities.We investigated the in vitro characterizations of morphology,size,zeta potential,drug loading,drug release behaviors,CD spectra,in vitro fluorescence/PA/CT/MR quadmodal imaging abilities and in vitro PTT/PDT effect.The cellular studies including uptake studies,cytotoxicities and ROS detection,and animal studies containing quadmodal imaging,PTT/PDT effect in vivo and synergistic PTT/PDT antitumor efficiency are also evaluated.The in vitro characterizations validated the successful construction of ICG-Au@BSA-Gd nanocomposites.The cellular and in vivo animal studies further illustrated the nanoplatform hold great promise for simultaneoustherapeutic monitoring and precise PTT/PDT cancer therapy.