Engineering Cu2-xS-conjugated upconverting nanocomposites for NIR-II light-induced enhanced chemodynamic/photothermal therapy of cancer.

The integration of chemodynamic therapy (CDT) and photothermal therapy (PTT) has played a huge role in improved anticancer treatments. Here, a novel multifunctional nanoplatform based on Cu2-xS conjugated NaYF4:Yb/Er@NaYF4:Yb upconversion nanoparticles (UCNPs) was proposed and designed. In the UCNPs-Cu2-xS nanocomposites, UCNPs with excellent luminescent properties and a high X-ray attenuation coefficient can serve as an upconversion luminescence (UCL) and computer tomography (CT) imaging contrast agent; meanwhile, Cu(II) in the Cu2-xS nanodots enables the nanocomposites to have a magnetic resonance imaging (MRI) ability owing to the presence of unpaired electrons. Moreover, the Cu2-xS nanodots with a strong absorbance in the NIR II biowindow not only could be employed as a stable photothermal agent under NIR laser irradiation, but also could be used as a photothermal-enhanced Fenton nanocatalyst to respond to over-expressed H2O2 in the tumor microenvironment (TME) and generate toxic hydroxyl radicals (˙OH) to effectively kill cancer cells. Furthermore, the UCNPs-Cu2-xS nanocomposites possess negligible cytotoxicity and a high photothermal conversion efficiency (43.8%) in the NIR-II biowindow (1064 nm), indicating that they possess great potential for the UCL/CT/MR multi-modal imaging guided synergistic enhanced CDT/PTT of cancer.

A highly active (102) surface-induced rapid degradation of a CuS nanotheranostic platform for in situ T1-weighted magnetic resonance imaging-guided synergistic therapy.

Polyvinylpyrrolidone-modified CuS nanocrystals (CuS NCs) with high photothermal conversion efficiency (46%) and pH and near-infrared (NIR) light-triggered degradation properties are a promising nanotheranostic platform for in situ magnetic resonance imaging (MRI)-guided synergistic photothermal and photodynamic therapy. On the one hand, the (102) surface of CuS NCs has a small bandgap based on density functional theory, which leads to high photothermal conversion efficiency. On the other hand, the S vacancy formation energy of the (102) surface is favourable. On entry into tumor cells through endocytosis, the S2- ions on the (102) surface of CuS NCs can be easily oxidized under the tumor microenvironment and 808 nm laser irradiation; then, a large amount of Cu+ ions can be released from CuS NCs and accelerate the degradation of nanocrystals. Cu+ ions can generate reactive oxygen species (ROS) under the tumor microenvironment and 808 nm laser irradiation. Meanwhile, the oxidation product Cu2+ ions can be generated from the oxidized Cu+ ions and applied for in situ T1-weighted magnetic resonance imaging. Moreover, the biodegradable CuS NCs possess a high tumor uptake and can be rapidly excreted with a low long-term retention/toxicity. Therefore, degradable and multifunctional CuS NCs are a safe and efficient candidate for the diagnosis and treatment of cancer.

Renal Clearable Bi-Bi2S3 Heterostructure Nanoparticles for Targeting Cancer Theranostics.

Recent development of precise nanomedicine has aroused an overwhelming interest in integration of diagnosis and treatment for cancers. Designing renal-clearable and targeting nanoparticles (NPs) has specific cancer theranostic implications and remains a challenging task. In this work, the ultrasmall folic acid (FA) and bovine serum albumin-modified Bi-Bi2S3 heterostructure nanoparticles NPs (Bi-Bi2S3/BSA&FA NPs) with excellent computed tomography (CT) and photoacoustic imaging abilities and outstanding photothermal performances were synthesized in an aqueous phase route via a simple method. Bi-Bi2S3/BSA&FA NPs have the following criteria: (i) Bi-Bi2S3/BSA&FA NPs with heterostructure possess better stability than Bi NPs and higher Bi content than Bi2S3 NPs, which are conducive to the enhancement of CT imaging effect; (ii) Bi-Bi2S3/BSA&FA NPs with FA molecules on the surface could target the tumor site effectively; (iii) Bi-Bi2S3/BSA&FA NPs could inhibit tumor growth effectively under 808 nm laser irradiation; (iv) ultrasmall Bi-Bi2S3/BSA&FA NPs could be cleared through kidney and liver within a reasonable time, avoiding a long-term retention/toxicity. Therefore, the renal clearable Bi-Bi2S3/BSA&FA NPs are a promising agent for targeting cancer theranostics.

Ultrafast synthesis of ultrasmall polyethylenimine-protected AgBiS2 nanodots by "rookie method" for in vivo dual-modal CT/PA imaging and simultaneous photothermal therapy.

Developing a biocompatible nanotheranostic platform integrating diagnostic and therapeutic functions is a great prospect for cancer treatment. However, it is still a great challenge to synthesize nanotheranostic agents using an ultra-facile method. In the research reported here, ultrasmall polyethylenimine-protected silver bismuth sulfide (PEI-AgBiS2) nanodots were successfully synthesized using an ultra-facile and environmentally friendly strategy (1 min only at room temperature), which could be described as a "rookie method". PEI-AgBiS2 nanodots show good monodispersity and biocompatibility. For the first time, PEI-AgBiS2 nanodots were reported as a powerful and safe nanotheranostic agent for cancer treatment. PEI-AgBiS2 nanodots exhibit excellent computed tomography (CT) and photoacoustic (PA) dual-modal imaging ability, which could effectively guide photothermal cancer therapy. Furthermore, PEI-AgBiS2 nanodots exhibit a high photothermal conversion efficiency (η = 35.2%). The photothermal therapy (PTT) results demonstrated a highly efficient tumor ablation ability. More importantly, the blood biochemistry and histology analyses verify that the PEI-AgBiS2 nanodots have negligible long-term toxicity. This work highlights that PEI-AgBiS2 nanodots produced using this extremely effective method are a high-performance and safe PTT agent. These findings open a new gateway for synthesizing nanotheranostic agents by using this ultra-facile method in the future.

Simple construction of Cu2-xS:Pt nanoparticles as nanotheranostic agent for imaging-guided chemo-photothermal synergistic therapy of cancer.

Synergistic therapy has attracted intense attention in medical treatment because it can make up for the disadvantages of single therapy and greatly improve the efficacy of cancer treatment. However, it remains a challenge to build a simple system to achieve synergistic therapy. In this study, X-ray computed tomography (CT) imaging-guided chemo-photothermal synergistic therapy can be easily achieved by simple construction of Cu2-xS:Pt(0.3)/PVP nanoparticles (NPs). Cu2-xS:Pt(0.3)/PVP NPs can passively accumulate within the tumor sites, thus ensuring that many Cu2-xS:Pt(0.3)/PVP NPs are brought into the tumor cells, which can be confirmed by the results of cellular uptake, imaging, and nanoparticle biodistribution. It can be verified that the platinum ions can be released from Cu2-xS:Pt(0.3)/PVP NPs under 808 nm laser irradiation. Simultaneously, Pt(iv) ions are reduced to Pt(ii) ions by excess glutathione and then, they exhibit chemo-anticancer activities. In addition, Cu2-xS:Pt(0.3)/PVP NPs can be used as an effective photothermal agent. The results demonstrate that the efficient tumor growth inhibition effect can be realized from the mice treated with Cu2-xS:Pt(0.3)/PVP NPs under 808 nm laser irradiation by chemo-photothermal synergistic therapy. Furthermore, Cu2-xS:Pt(0.3)/PVP NPs can be thoroughly cleared through feces in a short time, showing high biosafety for further potential clinical translations.

Multifunctional Cu-Ag2S nanoparticles with high photothermal conversion efficiency for photoacoustic imaging-guided photothermal therapy in vivo.

Photothermal therapy (PTT) has attracted increasing interest and become widely used in cancer therapy owing to its noninvasiveness and low level of systemic adverse effects. However, there is an urgent need to develop biocompatible and multifunctional PTT agents with high photothermal conversion efficiency. Herein, biocompatible Cu-Ag2S/PVP nanoparticles (NPs) with strong near-infrared absorption and high photothermal conversion efficiency were successfully synthesized for high-performance photoacoustic (PA) imaging-guided PTT in vivo. The novel Cu-Ag2S/PVP NPs feature high photothermal conversion efficiency (58.2%) under 808 nm light irradiation, noticeably higher than those of most reported PTT agents. Because of their good dispersibility, Cu-Ag2S/PVP NPs passively accumulate within tumors via the enhanced permeability and retention effect, which can be confirmed by PA imaging, photothermal performance, and biodistribution in vivo. Furthermore, Cu-Ag2S/PVP NPs are thoroughly cleared through feces and urine within seven days, indicating a high level of biosafety for further potential clinical translation.