Effect of PVP Molecular Weights on the Synthesis of Ultrasmall Cus Nanoflakes: Synthesis, Properties, and Potential Application for Phototheranostics.

Copper sulfide nanoparticles (CuS) hold tremendous potential for applications in photothermal therapy (PTT) and photoacoustic imaging (PAI). However, the conventional chemical coprecipitation method often leads to particle agglomeration issues. To overcome this challenge, we utilized polyvinylpyrrolidone (PVP) as a stabilizing agent, resulting in the synthesis of small PVP-CuS nanoparticles named PC10, PCK30, and PC40. Our study aimed to investigate how different molecular weights of PVP influence the nanoparticles' crystalline characteristics and essential properties, especially their photoacoustic and photothermal responses. While prior research on PVP-assisted CuS nanoparticles has been conducted, our study delves deeper into this area, providing insights into optical properties. Remarkably, all synthesized nanoparticles exhibited a crystalline structure, were smaller than 10 nm, and featured an absorbance peak at 1020 nm, indicating their robust photoacoustic and photothermal capabilities. Among these nanoparticles, PC10 emerged as the standout performer, displaying superior photoacoustic properties. Our photothermal experiments demonstrated significant temperature increases in all cases, with PC10 achieving an impressive efficiency of 51%. Moreover, cytotoxicity assays revealed the nanoparticles' compatibility with cells, coupled with an enhanced incidence of apoptosis compared to necrosis. These findings underscore the promising potential of PVP-stabilized CuS nanoparticles for advanced cancer theranostics.

Engineered photonic near-infrared light activated photothermal theranostic nanovaccine induced targeted remodeling of tumor microenvironment.

Tumor recurrence, which happens as a result of persisting tumor cells and minor lesions after treatments like surgery and chemotherapy, is a major problem in oncology. Herein, a strategy to combat this issue by utilize a theranostic nanovaccine composed of photonic HCuS. This nanovaccine aims to eradicate cancer cells and their traces while also preventing tumor recurrence via optimizing the photothermal immune impact. Successful membrane targeting allows for the introduction of new therapeutic agents into the tumor cells. Together with co-encapsulated Toll-Like Receptors (TLR7/8) agonist R848 for activating T cells and maturing DCs, the combined effects of HCuS and ICG function as photothermal agents that generate heat in the presence of NIR light. Photothermal-mediated immunotherapy with therapeutic modalities proved successful in killing tumor cells. By activating the immune system, this new photonic nanovaccine greatly increases immunogenic cell death (ICD), kills tumor cells, and prevents their recurrence.

Engineering of copper sulfide mediated by phototherapy performance.

Copper sulfide based phototherapy, including photothermal therapy and photodynamic therapy, is an emerging minimally invasive treatment of tumor, which the light was converted to heat or reactive oxygen to kill the tumor cells. Compared with conventional chemotherapy and radiation therapy, Cu2-x S based phototherapy is more efficient and has fewer side effects. However, considering the dose-dependent toxicity of Cu2-x S, the performance of Cu2-x S based phototherapy still cannot meet the requirement of the clinical application to now. To overcome this limitation, engineering of Cu2-x S to improve the phototherapy performance by increasing light absorption has attracted extensive attention. For better guidance of Cu2-x S engineering, we outline the currently engineering method being explored, including (1) structural engineering, (2) compositional engineering, (3) functional engineering, and (4) performance engineering. Also, the relationship between the engineering method and phototherapy performance was discussed in this review. In addition, the further development of Cu2-x S based phototherapy is prospected, including smart materials based phototherapy, phototherapy induced immune microenvironment modulation et al. This review will provide new ideas and opportunities for engineering of Cu2-x S with better phototherapy performance. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Recent advances in copper sulfide nanoparticles for phototherapy of bacterial infections and cancer.

Copper sulfide nanoparticles (CuS NPs) have attracted growing interest in biomedical research due to their remarkable properties, such as their high photothermal and thermodynamic capabilities, which are ideal for anticancer and antibacterial applications. This comprehensive review focuses on the current state of antitumor and antibacterial applications of CuS NPs. The initial section provides an overview of the various approaches to synthesizing CuS NPs, highlighting the size, shape and composition of CuS NPs fabricated using different methods. In this review, the mechanisms underlying the antitumor and antibacterial activities of CuS NPs in medical applications are discussed and the clinical challenges associated with the use of CuS NPs are also addressed.

Carboxymethyl ß-cyclodextrin grafted hollow copper sulfide@mesoporous silica carriers for stimuli-responsive pesticide delivery.

Stimuli-responsive controlled release systems have received extensive attention to improve the pesticide bioavailability and minimize environmental pollution. Herein, a multiple stimuli-responsive IMI@HCuS@mSiO2 @ -ss-CßCD delivery system was constructed using modified carboxymethyl ß-cyclodextrin (CßCD-ss-COOH) as sealing materials, hollow copper sulfide nanoparticles with amino-functionalized mesoporous silica shell (HCuS@mSiO2-NH2) as carriers and imidacloprid (IMI) as the model drug. The cavity structure of HCuS@mSiO2-NH2 would provide a large space for pesticide loading. The results revealed that HCuS@mSiO2-ss-CßCD was approximately 230 nm in size and the loading efficiency for IMI was 25.7%, and exhibited better biosafety on bacteria and seed. HCuS carriers were also served as photothermal agent and possessed high photothermal conversion effect (η = 38.4%). IMI@HCuS@mSiO2 @ -ss-CßCD displayed excellent foliage adhesion and multiple stimuli-responsive release properties to pH, α-amylase, GSH, and NIR. The photostability of IMI embedded in CuS@mSiO2 @ -ss-CßCD was approximately 10 times that of IMI solution. This work provides an efficient nanoplatform for realizing pesticide delivery.

Photothermal/lysozyme-catalyzed hydrolysis dual-modality therapy via halloysite nanotube-based platform for effective bacterial eradication.

Bacterial biofilm seriously impedes the healing of infected wound, remaining a major challenge in wound repair. Antibiotic-free antibacterial strategies based on nanotechnology are emerging as promising tools to combat bacterial infections. Here, halloysite nanotube (HNT), as a natural clay mineral, was employed to fabricate a multifunctional platform (designated as HNTs@CuS@PDA-Lys) through a layer-by-layer strategy for treating bacterial infections by utilizing synergistic lysozyme (Lys)-photothermal therapy (PTT). Specifically, amino-modified HNTs were first decorated with copper sulfide (CuS), followed by coated with a polydopamine (PDA) layer, then functionalized with antimicrobial enzyme Lys onto the surface of PDA via cation-π interactions. The as-prepared HNTs@CuS@PDA-Lys at a low dose (200 µg/mL) exhibited excellent synergistic Lys-photothermal bactericidal activity against Escherichia coli (E. coli) (100.0 ± 0.2 %) and Staphyloccocus aureus (S. aureus) (99.9 ± 0.1 %), eliminated 75.9 ± 2.0 % of S. aureus biofilm under near-infrared (NIR) irradiation (808 nm, 1.5 W/cm2). In vivo experiments using a S. aureus-infected rat model showed HNTs@CuS@PDA-Lys could rapidly kill bacteria and accelerate wound healing process. Overall, this multifunctional nanoplatform combines the advantages of PTT and Lys, providing a cost-efficient, environmental friendly strategy for bacterial and biofilm eradication, demonstrating the potential applications in the field of biomedicine.

Evaluation of citrus pectin capped copper sulfide nanoparticles against Candidiasis causing Candida biofilms.

The incidence of candidiasis has significantly increased globally in recent decades, and it is a significant source of morbidity and mortality, particularly in critically ill patients. Candida sp. ability to generate biofilms is one of its primary pathogenic traits. Drug-resistant strains have led to clinical failures of traditional antifungals, necessitating the development of a more modern therapy that can inhibit biofilm formation and enhance Candida sp. sensitivity to the immune system. The present study reports the anticandidal potential of pectin-capped copper sulfide nanoparticles (pCuS NPs) against Candida albicans. The pCuS NPs inhibit C. albicans growth at a minimum inhibitory concentration (MIC) of 31.25 µM and exhibit antifungal action by compromising membrane integrity and overproducing reactive oxygen species. The pCuS NPs, at their biofilm inhibitory concentration (BIC) of 15.63 µM, effectively inhibited C. albicans cells adhering to the glass slides, confirmed by light microscopy and scanning electron microscopy. Phase contrast microscopy pictures revealed that NPs controlled the morphological transitions between the yeast and hyphal forms by limiting conditions that led to filamentation and reducing hyphal extension. In addition, C. albicans showed reduced exopolysaccharide (EPS) production and exhibited less cell surface hydrophobicity (CSH) after pCuS NPs treatment. The findings suggest that pCuS NPs may be able to inhibit the emergence of virulence traits that lead to the formation of biofilms, such as EPS, CSH, and hyphal morphogenesis. The results raise the possibility of developing NPs-based therapies for C. albicans infections associated with biofilms.

Photothermal-triggered dendrimer nanovaccines boost systemic antitumor immunity.

Tumor vaccine that can effectively activate or strengthen the body's antitumor immune response to kill and eliminate tumor cells has attracted widespread attention. Currently developed tumor vaccines have severe shortcomings such as low bioavailability and lack of dual or multiple functions, resulting in poor antitumor efficacy. Herein, we report the development of an advanced nanosystem integrated with phenylboronic acid (PBA)-functionalized poly(amidoamine) dendrimers of generation 5 (G5), copper sulfide nanoparticles, and cyclic GMP-AMP (cGAMP), an immune adjuvant (for short, G5-PBA@CuS/cGAMP) to act as a photothermal-triggered nanovaccine. We show that the prepared functional nanosystem possesses an average CuS core size of 3.6 nm, prominent near-infrared absorption feature to have an excellent photothermal conversion efficiency of 44.0%, and good protein adsorption characteristics due to the PBA modification. With these features, the developed nanosystem can be adopted for photothermal therapy of primary melanoma tumors and simultaneously absorb the whole tumor cell antigens, thus creating photothermal-triggered dendrimeric nanovaccine of G5-PBA@CuS/cGAMP/antigen in situ to induce antitumor immune response to inhibit the distal tumors as well. Meanwhile, melanoma cells treated with the G5-PBA@CuS in vitro under laser irradiation allowed the creation of G5-PBA@CuS/antigen complexes that could be further integrated with cGAMP to form preformed nanovaccine for effective primary tumor inhibition and tumor occurrence prevention. The designed photothermal-triggered dendrimeric nanovaccine may represent an advanced nanomedicine formulation to effectively inhibit the growth of primary and distal tumors, and prevent tumor occurrence through the stimulated systemic antitumor immunity.

Gold nanobipyramid@copper sulfide nanotheranostics for image-guided NIR-II photo/chemodynamic cancer therapy with enhanced immune response.

Photothermal therapy (PTT), photodynamic therapy (PDT), and chemodynamic therapy (CDT) can cause cancer cell death through an immunogenic process. However, the study of second near-infrared window (NIR-II)-triggered PTT and PDT combined with CDT to induce an immune response has not been recently reported. Here, we integrated gold nanobipyramids and copper sulfide in a core/shell architecture (AuNBP@CuS). The material displays both photodynamic and photothermal properties under irradiation with a NIR-II laser. The released Cu2+ from CuS under an acidic tumor microenvironment can be converted to Cu+ by glutathione following a Fenton-like reaction with hydrogen peroxide to generate highly toxic hydroxyl radicals in the tumor region. Both in vitro and in vivo results demonstrated that such multifunctional nanoplatforms could achieve enhanced efficiency for image-guided tumor suppression based on the NIR-II photo/chemodynamic therapy. We found that damage-associated molecular pattern molecules such as adenosine triphosphate, pre-apoptotic calreticulin, and high mobility group box-1 in dying cells induced by the NIR-II photo/chemodynamic therapy could simultaneously trigger adaptive immune responses. This is the first report revealing that NIR-II photo/chemodynamic therapy based on AuNBP@CuS had promising performance on tumor suppressor with an effective immunogenic cell death process. STATEMENT OF SIGNIFICANCE: 1. AuNBP@CuS displays both NIR-II photodynamic and photothermal properties. 2. Cu+ following a Fenton-like reaction to generate highly toxic hydroxyl radicals. 3. The NIR-II photo/chemodynamic therapy can trigger adaptive immune responses. 4. Such multifunctional nanoplatforms could achieve enhanced efficiency for tumor suppression.

NIR laser-conjugated glutathione-coated Mn-doped CuS nanoprisms as photothermal agent for cancer treatment.

The cancer treatment by laser-conjugated nanomaterial has become a new developing trend due of their unique physicochemical performance. The previous few studies reported the preparation of undoped CuS nanoprisms. The current research was concerned with the Mn doping effect on the CuS nanoprisms and its activity in tumor toxicity of M.D. Anderson-Metastatic Breast 231 (MDA-MB-231) cell line with laser treatment. To prepare a novel CuS and Mn-doped CuS nanoprisms with high surface area by two-phase colloidal method, copper nitrate and sulfur powder were used as sources of copper and sulfur respectively. The prepared nanoprisms were investigated as antibacterial and photothermal agents in MDA-MB-231 cancer treatment using near-infrared (NIR) laser. The Mn-CuS nanoprisms were modified with glutathione (GSH) to decrease the cytotoxicity and increase the biocompatibility. The characterization of synthesized nanoprisms involved the structural, compositional, surface charges, optical, and morphological property analyses. X-ray diffraction (XRD) showed the peaks of hexagonal covellite copper sulfide nanoparticles and additional diffraction peaks at Mn-CuS which are assigned to orthorhombic chalcocite CuS. The transmission electron microscopy (TEM) images showed that the CuS and Mn-CuS nanoparticles have nanoprism morphology. The antibacterial activity test revealed that the activity enhances by doping and the prepared Mn-CuS nanostructures were more effective against the Staphylococcus aureus and Escherichia coli bacteria. The results of photothermal treatment indicated that the cancer cells were effectively killed and the GSH@Mn-CuS nanoprisms are able to be used as an efficient theranostic agent for tumor photothermal therapy in the future.

All-In-One Second Near-Infrared Light-Responsive Drug Delivery System for Synergistic Chemo-Photothermal Therapy.

Light-responsive nanocarrier-based drug delivery systems (NDDSs), due to their unique advantages such as safety, minimal cross-reaction, and spatiotemporal precision, have received wide attention. Notably, second near-infrared (NIR-II) light, which has a high penetration depth for manipulating NDDSs to release drugs, is in high demand. Herein, polyethylene glycol (PEG)-modified hollow CuxS nanoparticles (NPs) are developed as an all-in-one NIR-II light-responsive NDDS for synergistic chemo-photothermal therapy. First, CuxS-PEG NPs were prepared under mild conditions by using Cu2O NPs as sacrificial templates. The morphology, photothermal effect, drug loading/releasing abilities, and synergistic chemo-photothermal therapy of CuxS-PEG NPs have been investigated. The CuxS-PEG NPs with hollow structures showed a high drug loading capacity (∼255 µg Dox per mg of CuxS NPs) and stimuli-responsive drug release triggered by NIR-II laser irradiation. The synergistic chemo-photothermal therapy based on the Dox/CuxS-PEG NPs showed 98.5% tumor elimination. Our study emphasizes the great potential of CuxS-PEG NPs as an all-in-one NIR-II light-responsive NDDS for applications in biomedicine.

CuS NP-based nanocomposite with photothermal and augmented-photodynamic activity for magnetic resonance imaging-guided tumor synergistic therapy.

Although many treatments have been developed for oncotherapy, the lack of effective imaging guidance in the therapeutic process is still an urgent problem to be solved. In this study, magnetic resonance contrast agent (Gd) chelated on CuS nanoparticles and glucose oxidase (GOx) were coloaded into mesoporous silica nanoparticles (MSNs) to form GOx-Gd-CuS@MSNs, in which the Gd provided magnetic resonance imaging (MRI) for therapeutic process monitor while GOx could catalyze the generation of H2O2 to enhance the photodynamic therapy (PDT). The in vitro results show that under near-infrared (NIR) laser irradiation (2 W·cm-2, 5 min), temperature rapidly increased by approximately 30 °C for the accumulation of heat. At the same time, GOx on GOx-Gd-CuS@MSNs effectively consumed glucose to produce a large amount of H2O2, which was used to augment PDT through producing highly toxic hydroxyl radicals (·OH) and singlet oxygen (1O2). The photothermal and augmented-photodynamic could induce apoptosis and death of tumor cells. More importantly, the study found that GOx-Gd-CuS@MSNs had MRI performance, which provided imaging guidance during the treatment process, and it can monitor the diffusion of water molecules in the tumor tissue during the treatment and microcirculation perfusion of capillary network. These results indicate that the nanomaterial produced significant synergistic therapeutic effects through photothermal and photodynamic forces, meanwhile showed excellent spatial resolution and deep tissue penetration in imaging.

Magnetic Resonance/Infrared Dual-Modal Imaging-Guided Synergistic Photothermal/Photodynamic Therapy Nanoplatform Based on Cu1.96S-Gd@FA for Precision Cancer Theranostics.

Developing new nanoplatforms for dynamically and quantitatively visualizing drug accumulation and targeting within tumors is crucial for precision cancer theranostic. However, achieving efficient tumor therapy via synergistic photothermal/photodynamic therapy (PTT/PDT) using a single excitation light source, remains a challenge. In this work, we designed Gd-surface functionalized copper sulfide nanoparticles that were modified with folic acid (FA) (Cu1.96S-Gd@FA) to overcome the above limitations and promote PTT/PDT therapeutics. Here, Cu1.96S-Gd nanoparticles were synthesized via a coprecipitation method. All samples exhibited high longitudinal relaxivity (up to 12.9 mM-1 s-1) and strong photothermal conversion efficiency (50.6%). Furthermore, the Gd ions promoted electron-hole segregation, inducing the Cu1.96S-Gd nanoparticles to generate more reactive oxygen species (ROS) than pure Cu1.96S nanoparticles. The Cu1.96S-Gd@FA enabled the targeting of folate receptor (FR) and promoted cellular uptake, consequently enhancing oncotherapy efficacy. Compared to non-targeted Cu1.96S-Gd, a higher signal enhancement for magnetic resonance (MR) imaging in vivo by Cu1.96S-Gd@FA was recorded. Given photothermal ability, the nanoparticles also could be visualized in infrared (IR) imaging. Furthermore, the nanoparticles exhibited biodegradation behavior and achieved good drug elimination performance via renal clearance. Our strategy, integrating Cu1.96S-Gd@FA nanoparticles, MR/IR dual-modal imaging, and PTT/PDT into one nanoplatform, demonstrated great potential for anti-breast cancer therapy by effectively targeting FR overexpressed breast cancer cells.

Self-assembled semiconducting polymer based hybrid nanoagents for synergistic tumor treatment.

There is an impending need for the development of carrier-free nanosystems for single laser triggered activation of phototherapy, as such approach can overcome the drawbacks associated with irradiation by two distinct laser sources for avoiding prolonged treatment time and complex treatment protocols. Herein, we developed a self-assembled nanosystem (SCP-CS) consisting of a new semiconducting polymer (SCP) and encapsulated ultrasmall CuS (CS) nanoparticles. The SCP component displays remarkable near infrared (NIR) induced photothermal ability, enhanced reactive oxygen species (ROS) generation, and incredible photoacoustic (PA) signals upon activation by 808 nm laser for phototherapy mediated cancer ablation. The CuS component improves the PA imaging ability of SCP-CS, and also enhances photo-induced chemodynamic efficacy. Attributed to promoted single laser-triggered hyperthermia and enhanced ROS generation, the SCP-CS nanosystem shows effective intracellular uptake and intratumoral accumulation, enhanced tumor suppression with reduced treatment time, and devoid of any noticeable toxicity.

Remote Photothermal Control of DNA Origami Assembly in Cellular Environments.

In situ synthesis of DNA origami structures in living systems is highly desirable due to its potential in biological applications, which nevertheless is hampered by the requirement of thermal activation procedures. Here, we report a photothermal DNA origami assembly method in near-physiological environments. We find that the use of copper sulfide nanoparticles (CuS NPs) can mediate efficient near-infrared (NIR) photothermal conversion to remotely control the solution temperature. Under a 4 min NIR illumination and subsequent natural cooling, rapid and high-yield (>80%) assembly of various types of DNA origami nanostructures is achieved as revealed by atomic force microscopy and single-molecule fluorescence resonance energy transfer analysis. We further demonstrate the in situ assembly of DNA origami with high location precision in cell lysates and in cell culture environments.

Dual Plasmonic Au-Cu2-x S Nanocomposites: Design Strategies and Photothermal Properties.

Coupling two different materials to create a hybrid nanostructured system is a powerful strategy for achieving synergistically enhanced properties and advanced functionalities. In the case of Au and Cu2-x S, their combination on the nanoscale results in dual plasmonic Au-Cu2-x S nanocomposites that exhibit intense photon absorption in both the visible and the near-infrared spectral ranges. Their strong light-absorbing properties translate to superior photothermal transduction efficiency, making them attractive in photothermal-based applications. There are several nanostructure configurations that are possible for the Au-Cu2-x S system, and the successful fabrication of a particular architecture often requires a carefully planned synthetic strategy. In this Minireview, the different synthetic approaches that can be employed to produce rationally designed Au-Cu2-x S nanocomposites are presented, with a focus on the experimental protocols that can lead to heterodimer, core-shell, reverse core-shell, and yolk-shell configurations. The photothermal behavior of these materials is also discussed, providing a glimpse of their potential use as photothermally active agents in therapeutic and theranostic applications.

Inclusion of dicopper oxide instead of copper sulfate in diets for growing-finishing pigs results in greater final body weight and bone mineralization, but reduced accumulation of copper in the liver.

An experiment was conducted to test the hypothesis that inclusion of Cu oxide (Cu2O) in diets for growing-finishing pigs improves body weight (BW) and bone mineralization, and reduces accumulation of Cu in the liver compared with pigs fed diets containing Cu sulfate (CuSO4). Two hundred growing pigs (initial BW: 11.5 ± 0.98 kg) were allotted to a randomized complete block design with 2 blocks of 100 pigs, 5 dietary treatments, 5 pigs per pen, and a total of 8 pens per treatment. Treatments included the negative control (NC) diet that contained 20 mg Cu/kg, and 4 diets in which 125 or 250 mg Cu/kg from CuSO4 or Cu2O were added to the NC diet. The experiment was divided into 4 phases and concluded when pigs reached market weight. Pig weights were recorded on day 1 and at the end of each phase and feed provisions were recorded throughout the experiment. On the last day of phases 1 and 4, 1 pig per pen was sacrificed to obtain samples of liver and spleen tissue, and the right metacarpal was collected. Results indicated that pigs fed diets containing 250 mg Cu/kg from CuSO4 had greater BW at the end of phases 1 and 2 than pigs fed NC diets. Pigs fed diets containing 250 mg Cu/kg from Cu2O had greater (P < 0.05) BW at the end of phases 1, 2, 3, and 4 compared with pigs fed NC diets, and these pigs also had greater BW at the end of phases 3 and 4 than pigs fed all other diets. Pigs fed the diets with 250 mg Cu/kg tended to have greater (P < 0.10) feed intake than pigs fed the NC diet at the end of phase 2, and for the overall experimental period, pigs fed diets containing 250 mg Cu/kg from Cu2O had greater (P < 0.05) feed intake than pigs on all other treatments. However, no differences in gain:feed ratio were observed among treatments. Copper accumulation in liver and spleen increased with Cu dose, but at the end of phase 1, pigs fed 250 mg Cu/kg from CuSO4 had greater (P < 0.05) Cu concentration in liver and spleen than pigs fed 250 mg Cu/kg from Cu2O. Pigs fed diets containing 250 mg Cu/kg from Cu2O had greater (P < 0.05) quantities of bone ash and greater (P < 0.05) concentrations of Ca, P, and Cu in bone ash than pigs fed NC diets or the 2 diets containing CuSO4, but Zn concentration in bone ash was less (P < 0.05) in pigs fed diets containing 250 mg Cu/kg from Cu2O. To conclude, supplementing diets for growing pigs with Cu2O improves growth performance and bone mineralization with less Cu accumulation in liver compared with pigs fed diets containing CuSO4.

Hollow Mesoporous Silica Nanoparticles Gated by Chitosan-Copper Sulfide Composites as Theranostic Agents for the Treatment of Breast Cancer.

The combination of chemotherapy and photothermal therapy (PTT) into a single formulation has attracted increasing attention as a strategy for enhancing cancer treatment. Here, hollow mesoporous silica nanoparticles (HMSNs) were used as a base carrier material, loaded with the anti-cancer drug doxorubicin (DOX), and surface functionalized with chitosan (CS) and copper sulfide (CuS) nanodots to give HMSNs-CS-DOX@CuS. In this formulation, the CuS dots act as gatekeepers to seal the surface pores of the HMSNs, preventing a burst release of DOX into the systemic circulation. S-S bonds connect the CuS dots to the HMSNs; these are selectively cleaved under the reducing microenvironment of the tumor, permitting targeted drug release. This, coupled with the PTT properties of CuS, results in a potent chemo/PTT platform. The HMSNs-CS-DOX@CuS nanoparticles have a uniform size (150 ± 13 nm), potent photothermal properties (η = 36.4 %), and tumor-targeted and near infrared (NIR) laser irradiation-triggered DOX release. In vitro and in vivo experimental results confirmed that the material has good biocompatibility, but is effectively taken up by cancer cells. Moreover, the CuS nanodots permit simultaneous thermal/photoacoustic dual-modality imaging. Treatment with HMSNs-CS-DOX@CuS and NIR irradiation caused extensive apoptosis in cancer cells both in vitro and in vivo, and could dramatically extend the lifetimes of animals in a murine breast cancer model. The system developed in this work therefore merits further investigation as a potential nanotheranostic platform for cancer treatment. STATEMENT OF SIGNIFICANCE: Conventional cancer chemotherapy is accompanied by unavoidable off-target toxicity. Combination therapies, which can ameliorate these issues, are attracting significant attention. Here, the anticancer drug doxorubicin (DOX) was encapsulated in the central cavity of chitosan (CS)-modified hollow mesoporous silica nanoparticles (HMSNs). The prepared system can target drug release to the tumor microenvironment. When exposed to near infrared laser (NIR) irradiation, CuS nanodots located at the surface pores of the HMSNs generate energy, accelerating drug release. In addition, a systematic in vitro and in vivo evaluation confirmed the HMSNs-CS-DOX@CuS platform to give highly effective synergistic chemotherapeutic-photothermal therapy and have effective thermal/photoacoustic dual-imaging properties. This work may open up a new avenue for NIR-enhanced synergistic therapy with simultaneous thermal/photoacoustic dual imaging.

Antifouling Dendrimer-Entrapped Copper Sulfide Nanoparticles Enable Photoacoustic Imaging-Guided Targeted Combination Therapy of Tumors and Tumor Metastasis.

The development of functional intelligent theranostic nanoplatform for imaging-directed synchronous inhibition of primary tumor and tumor metastasis is still a challenging task. We present here the creation of functional dendrimer-entrapped CuS nanoparticles (CuS DENPs) complexed with plasmid DNA-encoding hypermethylation in cancer 1 (pDNA-HIC1) for photoacoustic (PA) imaging-directed simultaneous inhibition of tumors and tumor metastasis. Poly(amidoamine) dendrimers of generation 5 were covalently attached with 1,3-propane sultone and arginine-glycine-aspartic acid (RGD) peptide through a spacer of poly(ethylene glycol) and adopted for the templated synthesis of CuS NPs. The prepared functional RGD-CuS DENPs possess a mean CuS core diameter of 4.2 nm, good colloidal stability, and an excellent absorption feature in the second near-infrared window, thus having a photothermal conversion efficiency of 49.8% and an outstanding PA imaging capability. The functional DENPs can effectively deliver pDNA-HIC1 to prevent cancer cell invasion and metastasis in a serum-enhancing manner by virtue of zwitterionic modification-rendered antifouling property. The developed RGD-CuS DENPs/pDNA polyplexes display αvß3 integrin-targeted enhanced anticancer activity through the combined CuS NP-mediated photothermal therapy (PTT) and pDNA delivery-rendered cancer cell metastasis inhibition. This can also be proven by the therapeutic efficacy of a triple-negative breast cancer model in vivo, where inhibition of both the primary subcutaneous tumor and lung metastasis can be realized. The created dendrimer-CuS hybrid nanoplatform represents one of the updated designs of nanomedicine for PA imaging-directed combination PTT/gene therapy of tumors and tumor metastasis.

[Photothermal effect of nano-copper sulfide against tongue squamous cell carcinoma].

OBJECTIVE: To investigate the anti-tumor effect of BSA@CuS-PEG nanocomposites on tongue squamous cell carcinoma. METHODS: Transmission electron microscopy, dynamic light scattering, Zeta potential and ultraviolet absorption spectroscopy were used to characterize the synthesized BSA@CuS-PEG nanocomposite, whose photothermal properties was assessed with near infrared Ⅱ region excitation light (1064 nm). The cytotoxicity of the nanocomposite in Cal27 and SCC9 cells was evaluated using CCK-8 assay, and its effect on cell cycle distribution was analyzed using flow cytometry. The in vivo antitumor effect of BSA@CuS-PEG was investigated in a Balb/c mouse model bearing subcutaneous Cal27 tumor xenograft. RESULTS: The synthesized BSA@CuS-PEG nanocomposite showed a temperature variation (ΔT) of about 30 ℃ under near-infrared (NIR) irradiation (0.5 W/cm2), suggesting its excellent photothermal sensitivity. CCK-8 assay showed that BSA@CuS-PEG had no significant toxicity to tumor cells, but upon NIR irradiation, the nanocomposite produced a significant stronger inhibitory effect on Cal27 and SCC9 cells than free nanocomposites (P < 0.001). Cell cycle analysis showed that compared with free nanocomposites, BSA@CuS-PEG plus NIR irradiation caused more obvious cell cycle arrest at G2/M phase in tongue cancer cells (P < 0.001). In the tumor-bearing mice, BSA@CuS-PEG combined with NIR irradiation produced a significant anti-tumor effect as compared with saline treatment plus NIR irradiation (P < 0.001). CONCLUSION: The BSA@CuS-PEG nanocomposite shows prominent photothermal properties and good anti-tumor effects both in vivo and in vitro, and thus provides a promising method for non-invasive early diagnosis and non-surgical treatment of primary tongue cancer.