The Graphene Quantum Dots Gated Nanoplatform for Photothermal-Enhanced Synergetic Tumor Therapy.

Currently, the obvious side effects of anti-tumor drugs, premature drug release, and low tumor penetration of nanoparticles have largely reduced the therapeutic effects of chemotherapy. A drug delivery vehicle (MCN-SS-GQDs) was designed innovatively. For this, the mesoporous carbon nanoparticles (MCN) with the capabilities of superior photothermal conversion efficiency and high loading efficiency were used as the skeleton structure, and graphene quantum dots (GQDs) were gated on the mesopores via disulfide bonds. The doxorubicin (DOX) was used to evaluate the pH-, GSH-, and NIR-responsive release performances of DOX/MCN-SS-GQDs. The disulfide bonds of MCN-SS-GQDs can be ruptured under high glutathione concentration in the tumor microenvironment, inducing the responsive release of DOX and the detachment of GQDs. The local temperature of a tumor increases significantly through the photothermal conversion of double carbon materials (MCN and GQDs) under near-infrared light irradiation. Local hyperthermia can promote tumor cell apoptosis, accelerate the release of drugs, and increase the sensitivity of tumor cells to chemotherapy, thus increasing treatment effect. At the same time, the detached GQDs can take advantage of their extremely small size (5-10 nm) to penetrate deeply into tumor tissues, solving the problem of low permeability of traditional nanoparticles. By utilizing the photothermal properties of GQDs, synergistic photothermal conversion between GQDs and MCN was realized for the purpose of synergistic photothermal treatment of superficial and deep tumor tissues.

Green synthesis of quince/pectin cross-linked superporous hydrogel sponges for pH-regulated sustained domperidone delivery.

The present study aims to utilize green synthesis to fabricate stimuli-responsive, smart, quince/pectin cross-linked hydrogel sponges for the pH-regulated conveyance of domperidone. The designed hydrogel sponges were evaluated for a sol-gel fraction (%), swelling studies and kinetics, drug loading (%), electrolyte-responsive character, scanning electron microscopy (SEM), thermal analysis, drug-excipient compatibility studies (FTIR), X-ray diffraction (XRD) analysis, mechanical testing, in-vitro drug release studies, and acute oral toxicity studies. The drug loading (%) ranged from 67 to 85%. Hydrogel sponges displayed pH-responsive swelling potential, with optimum swelling in a phosphate buffer (pH 7.4) and insignificant swelling in an acidic buffer of pH 1.2. The prepared hydrogel sponges displayed second-order swelling dynamics. The FTIR data revealed the successful fabrication of the hydrogel sponges with the primary drug peaks remaining unchanged, demonstrating excipients-drug compatibility. SEM confirmed the rough, porous surface of hydrogel sponges with numerous cracks. XRD measurements revealed the transformation of the crystalline nature of domperidone into an amorphous one within the developed hydrogel sponges. Dissolution studies revealed little domperidone release in an acidic environment. However, hydrogel sponges exhibited release up to 10 h in phosphate buffer.The sponge's non-toxic or biocompatible character was confirmed through toxicological studies. Thus, the finding indicates that quince/pectin cross-linked hydrogel sponges are durable enough to deliver the domperidone to the gut for a longer time.

Targeted drug delivery systems for elemene in cancer therapy: The story thus far.

Elemene (ELE) is a group of broad-spectrum anticancer active ingredients with low toxicity extracted from traditional Chinese medicines (TCMs), such as Curcumae Rhizoma and Curcuma Radix, which can exert antitumour activities by regulating various signal pathways and targets. However, the strong hydrophobicity, short half-life, low bioavailability and weak in vivo targeting ability of ELE restrict its use. Targeted drug delivery systems based on nanomaterials are among the most viable methods to overcome these shortcomings. In this review, we first summarize recent studies on the clinical uses of ELE as an adjunct antitumour drug. ELE-based combination strategies have great promise for enhancing efficacy, reducing adverse reactions, and improving patients' quality of life and immune function. Second, we summarize recent studies on the antitumour mechanisms of ELE and ELE-based combination strategies. The potential mechanisms include inducing pyroptosis and ferroptosis, promoting senescence, regulating METTL3-mediated m6A modification, suppressing the Warburg effect, and inducing apoptosis and cell cycle arrest. Most importantly, we comprehensively summarize studies on the combination of targeted drug delivery systems with ELE, including passively and actively targeted drug delivery systems, stimuli-responsive drug delivery systems, and codelivery systems for ELE combined with other therapies, which have great promise in improving drug bioavailability, increasing drug targeting ability, controlling drug release, enhancing drug efficacy, reducing drug adverse effects and reversing MDR. Our summary will provide a reference for the combination of TCMs such as ELE with advanced targeted drug delivery systems in the future.

Dual Stimuli-Responsive Micelles for Imaging-Guided Mitochondrion-Targeted Photothermal/Photodynamic/Chemo Combination Therapy-Induced Immunogenic Cell Death.

Introduction: As the special modality of cell death, immunogenic cell death (ICD) could activate immune response. Phototherapy in combination with chemotherapy (CT) is a particularly efficient tumor ICD inducing method that could overcome the defects of monotherapies. Methods: In this study, new dual stimuli-responsive micelles were designed and prepared for imaging-guided mitochondrion-targeted photothermal/photodynamic/CT combination therapy through inducing ICD. A dual-sensitive methoxy-polyethylene glycol-SS-poly(L-γ-glutamylglutamine)-SS-IR780 (mPEG-SS-PGG-SS-IR780) polymer was synthesized by grafting IR780 with biodegradable di-carboxyl PGG as the backbone, and mPEG-SS-PGG-SS-IR780/paclitaxel micelles (mPEG-SS-PGG-SS-IR780/PTXL MCs) were synthesized by encapsulating PTXL in the hydrophobic core. Results: In-vivo and -vitro results demonstrated that the three-mode combination micelles inhibited tumor growth and enhanced the therapeutic efficacy of immunotherapy. The dual stimuli-responsive mPEG-SS-PGG-SS-IR780/PTXL MCs were able to facilitate tumor cell endocytosis of nanoparticles. They were also capable of promoting micelles disintegration and accelerating PTXL release. The mPEG-SS-PGG-SS-IR780/PTXL MCs induced mitochondrial dysfunction by directly targeting the mitochondria, considering the thermo- and reactive oxygen species (ROS) sensitivity of the mitochondria. Furthermore, the mPEG-SS-PGG-SS-IR780/PTXL MCs could play the diagnostic and therapeutic roles via imaging capabilities. Conclusion: In summary, this study formulated a high-efficiency nanoscale platform with great potential in combined therapy for tumors through ICD.

[Progress in stimuli-responsive molecularly imprinted polymers for enrichment analysis of trace components in traditional Chinese medicine].

Molecularly imprinted polymers demonstrate outstanding performance in the research on trace ingredients because of their high selectivity. Stimuli-responsive molecularly imprinted polymers(STR-MIPs) with the introduction of different responsive groups on the basis of traditionally imprinted materials can undergo reversible transformations when exposed to external stimuli such as temperature, magnetism, pH or light. Such responsiveness, combined with the specific recognition, endows STR-MIPs with excellent perfor-mance in trace component studies. Traditional Chinese medicine(TCM) contains complex components with trace content, and thus STR-MIPs have broad application prospects in the enrichment analysis of trace components in TCM. This paper elaborates on the application of STR-MIPs in the enrichment analysis of trace components in TCM from the perspectives of different stimuli, summarized relevant research achievements in the recent five years to broaden the application fields of molecular imprinting, and proposed a few opi-nions about their future development.

Three-pronged attacks by hybrid nanoassemblies involving a natural product, carbon dots, and Cu2+ for synergistic HCC therapy.

Tumor microenvironment (TME) stimuli-responsive nanoassemblies are emerging as promising drug delivery systems (DDSs), which acquire controlled release by structural transformation under exogenous stimulation. However, the design of smart stimuli-responsive nanoplatforms integrated with nanomaterials to achieve complete tumor ablation remains challenging. Therefore, it is of utmost importance to develop TME-based stimuli-responsive DDSs to enhance drug-targeted delivery and release at tumor sites. Herein, we proposed an appealing strategy to construct fluorescence-mediated TME stimulus-responsive nanoplatforms for synergistic cancer therapy by assembling photosensitizers (PSs) carbon dots (CDs), chemotherapeutic agent ursolic acid (UA), and copper ions (Cu2+). First, UA nanoparticles (UA NPs) were prepared by self-assembly of UA, then UA NPs were assembled with CDs via hydrogen bonding force to obtain UC NPs. After combining with Cu2+, the resulting particles (named UCCu2+ NPs) exhibited quenched fluorescence and photosensitization due to the aggregation of UC NPs. Upon entering the tumor tissue, the photodynamic therapy (PDT) and the fluorescence function of UCCu2+ were recovered in response to TME stimulation. The introduction of Cu2+ triggered the charge reversal of UCCu2+ NPs, thereby promoting lysosomal escape. Furthermore, Cu2+ resulted in additional chemodynamic therapy (CDT) capacity by reacting with hydrogen peroxide (H2O2) as well as by consuming glutathione (GSH) in cancer cells through a redox reaction, hence magnifying intracellular oxidative stress and enhancing the therapeutic efficacy due to reactive oxygen species (ROS) therapy. In summary, UCCu2+ NPs provided an unprecedented novel approach for improving the therapeutic efficacy through the three-pronged (chemotherapy, phototherapy, and heat-reinforced CDT) attacks to achieve synergistic therapy.

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.

Nano-mediated strategy for targeting and treatment of non-small cell lung cancer (NSCLC).

Lung cancer is the most common type of cancer, with over 2.1 million cases diagnosed annually worldwide. It has a high incidence and mortality rate, leading to extensive research into various treatment options, including the use of nanomaterial-based carriers for drug delivery. With regard to cancer treatment, the distinct biological and physico-chemical features of nano-structures have acquired considerable impetus as drug delivery system (DDS) for delivering medication combinations or combining diagnostics and targeted therapy. This review focuses on the use of nanomedicine-based drug delivery systems in the treatment of lung cancer, including the use of lipid, polymer, and carbon-based nanomaterials for traditional therapies such as chemotherapy, radiotherapy, and phototherapy. The review also discusses the potential of stimuli-responsive nanomaterials for drug delivery in lung cancer, and the limitations and opportunities for improving the design of nano-based materials for the treatment of non-small cell lung cancer (NSCLC).

Nanobiotechnological approaches in osteosarcoma therapy: Versatile (nano)platforms for theranostic applications.

Constructive achievements in the field of nanobiotechnology and their translation into clinical course have led to increasing attention towards evaluation of their use for treatment of diseases, especially cancer. Osteosarcoma (OS) is one of the primary bone malignancies that affects both males and females in childhood and adolescence. Like other types of cancers, genetic and epigenetic mutations account for OS progression and several conventional therapies including chemotherapy and surgery are employed. However, survival rate of OS patients remains low and new therapies in this field are limited. The purpose of the current review is to provide a summary of nanostructures used in OS treatment. Drug and gene delivery by nanoplatforms have resulted in an accumulation of therapeutic agents for tumor cell suppression. Furthermore, co-delivery of genes and drugs by nanostructures are utilized in OS suppression to boost immunotherapy. Since tumor cells have distinct features such as acidic pH, stimuli-responsive nanoparticles have been developed to appropriately target OS. Besides, nanoplatforms can be used for biosensing and providing phototherapy to suppress OS. Furthermore, surface modification of nanoparticles with ligands can increase their specificity and selectivity towards OS cells. Clinical translation of current findings suggests that nanoplatforms have been effective in retarding tumor growth and improving survival of OS patients.

Chitosan-based nanoscale systems for doxorubicin delivery: Exploring biomedical application in cancer therapy.

Green chemistry has been a growing multidisciplinary field in recent years showing great promise in biomedical applications, especially for cancer therapy. Chitosan (CS) is an abundant biopolymer derived from chitin and is present in insects and fungi. This polysaccharide has favorable characteristics, including biocompatibility, biodegradability, and ease of modification by enzymes and chemicals. CS-based nanoparticles (CS-NPs) have shown potential in the treatment of cancer and other diseases, affording targeted delivery and overcoming drug resistance. The current review emphasizes on the application of CS-NPs for the delivery of a chemotherapeutic agent, doxorubicin (DOX), in cancer therapy as they promote internalization of DOX in cancer cells and prevent the activity of P-glycoprotein (P-gp) to reverse drug resistance. These nanoarchitectures can provide co-delivery of DOX with antitumor agents such as curcumin and cisplatin to induce synergistic cancer therapy. Furthermore, co-loading of DOX with siRNA, shRNA, and miRNA can suppress tumor progression and provide chemosensitivity. Various nanostructures, including lipid-, carbon-, polymeric- and metal-based nanoparticles, are modifiable with CS for DOX delivery, while functionalization of CS-NPs with ligands such as hyaluronic acid promotes selectivity toward tumor cells and prevents DOX resistance. The CS-NPs demonstrate high encapsulation efficiency and due to protonation of amine groups of CS, pH-sensitive release of DOX can occur. Furthermore, redox- and light-responsive CS-NPs have been prepared for DOX delivery in cancer treatment. Leveraging these characteristics and in view of the biocompatibility of CS-NPs, we expect to soon see significant progress towards clinical translation.

Smart Metabolism Nanovalve Reprograms Cancer Energy Homeostasis for Maximizing Photometabolism Therapy.

Better understanding of important roles of metabolic reprogramming in therapeutic resistance provides insights into advancing cancer treatment. Herein, we present a photoactive metabolic reprogramming strategy (termed as photometabolism therapy, PMT), in which photoregulation of mitochondria leads to cancer cell metabolic crisis, and consequently overcomes therapeutic resistance while improving treatment efficacy. In specific, a stimuli-responsive metabolism NanoValve is developed for improving cascade cancer therapy through blocking mitochondrial energy supply. NanoValve is composed of an onion-like architecture with a gold nanorod core, a mesoporous silica shell encapsulating photosensitizer chlorin e6 and oxygen-saturated perfluorocarbon, and cationic liposomal coating with MMP2-cleavable polyethylene glycol corona, which together initiate mitochondria-specific PMT. NanoValve selectively responds to tumor-overexpressed MMP2 and achieves size decrease and charge reversal, which consequently enhances tumor penetration, cancer cell uptake, endosome escape, and most critically, mitochondrial accumulation. Importantly, NanoValve-mediated phototherapy can strongly destruct mitochondrial energy metabolism, thereby minimizing therapy resistance. Particularly, perfluorocarbon supplies oxygen to further overcome the tumor hypoxia-associated therapeutic barrier and maximizes synergistic anticancer effects. In vivo studies show that NanoValve can effectively eliminate tumors without side effects, thereby dramatically prolonging the survival of tumor-bearing mice. Thus, NanoValve provides a modular PMT approach and has the potential of advancing the treatment of malignancy.

Dual-stimuli responsive smart nanoprobe for precise diagnosis and synergistic multi-modalities therapy of superficial squamous cell carcinoma.

BACKGROUND: Although the promising advancements of current therapeutic approaches is available for the squamous cell carcinoma (SCC) patients, the clinical treatment of SCC still faces many difficulties. The surgical irreparable disfigurement and the postoperative wound infection largely hamper the recovery, and the chemo/radiotherapy leads to toxic side effects. RESULTS: Herein, a novel pH/Hyaluronidase (HAase) dual-stimuli triggered smart nanoprobe FeIIITA@HA has been designed through the biomineralization of Fe3+ and polyphenol tannic acid (TA) under the control of hyaluronic acid (HA) matrix. With the HA residues on the outer surface, FeIIITA@HA nanoprobes can specifically target the SCC cells through the over-expressed CD44, and accumulate in the carcinoma region after intravenously administration. The abundant HAase in carcinoma microenvironment will trigger the degradation of HA molecules, thereby exposing the FeIIITA complex. After ingesting by tumor cells via CD44 mediated endocytosis, the acidic lysosomal condition will further trigger the protonation of TA molecules, finally leading to the Fe3+ release of nanoprobe, and inducing a hybrid ferroptosis/apoptosis of tumor cells through peroxidase activity and glutathione depletion. In addition, Owing to the outstanding T1 magnetic resonance imaging (MRI) performance and phototermal conversion efficiency of nanoprobes, the MRI-guided photothermal therapy (PTT) can be also combined to complement the Fe3+-induced cancer therapy. Meanwhile, it was also found that the nanoprobes can promote the recruitment of CD4+ and CD8+ T cells to inhibit the tumor growth through the cytokines secretion. In addition, the FeIIITA@HA nanoprobes can be eliminated from the body and no obvious adverse side effect can be found in histological analysis, which confirmed the biosafety of them. CONCLUSION: The current FeIIITA@HA nanoprobe has huge potential in clinical translation in the field of precise diagnosis and intelligent synergistic therapy of superficial SCC. This strategy will promisingly avoid the surgical defects, and reduce the systemic side effect of traditional chemotherapy, paving a new way for the future SCC treatment.

Blood-brain Barrier Permeable and Multi-stimuli Responsive Nanoplatform for Orthotopic Glioma Inhibition by Synergistic Enhanced Chemo-/Chemodynamic/Photothermal/Starvation Therapy.

Glioblastoma (GBM) is a common malignant tumor in brain, and the treatment is still a challenge owing to the high invasiveness and the existence of blood-brain barrier (BBB). Although temozolomide (TMZ) is the first line medication, its efficacy is not ideal, which is related to the defect of dose distribution and drug resistance. It is urgent to develop a novel BBB-permeable nanoagent with multiple therapeutic modalities for improving the treatment effect of GBM. In this work, we constructed an intelligent BBB-permeable nanoplatform (CTHG-Lf NPs) with hollow mesoporous copper sulfide nanoparticles (HM-CuS NPs) as temozolomide (TMZ) carrier and hyaluronic acid (HA) as gatekeeper, as well as further modification with glucose oxidase (GOx) and lactoferrin (Lf) for highly efficient synergistic therapy of orthotopic GBM. The modification of Lf endows CTHG-Lf NPs with good target and BBB-permeable ability. HA not only prevents the TMZ leakage during circulation, but also achieves responsive drug release at tumor site for effective chemotherapy (CT). GOx provides high hydrogen peroxide (H2O2) and gluconic acid for improving the treatment effect of chemodynamic therapy (CDT), and realizes the starvation therapy (ST) by consuming glucose. The good photothermal effect of CTHG-Lf NPs achieves the "mild" photothermal therapy (PTT), while enhancing the efficiency of Fenton-like reaction. The synergistic strategy with CT/CDT/PTT/ST can not only promote brain drug delivery, but also realize the combination of multiple mechanisms for effective tumor growth suppression in vivo.

Progress in stimuli-responsive molecularly imprinted polymers for enrichment analysis of trace components in traditional Chinese medicine / 中国中药杂志

Molecularly imprinted polymers demonstrate outstanding performance in the research on trace ingredients because of their high selectivity. Stimuli-responsive molecularly imprinted polymers(STR-MIPs) with the introduction of different responsive groups on the basis of traditionally imprinted materials can undergo reversible transformations when exposed to external stimuli such as temperature, magnetism, pH or light. Such responsiveness, combined with the specific recognition, endows STR-MIPs with excellent perfor-mance in trace component studies. Traditional Chinese medicine(TCM) contains complex components with trace content, and thus STR-MIPs have broad application prospects in the enrichment analysis of trace components in TCM. This paper elaborates on the application of STR-MIPs in the enrichment analysis of trace components in TCM from the perspectives of different stimuli, summarized relevant research achievements in the recent five years to broaden the application fields of molecular imprinting, and proposed a few opi-nions about their future development.

Photo-Stimuli-Responsive CuS Nanomaterials as Cutting-Edge Platform Materials for Antibacterial Applications.

Photo-stimuli-responsive therapeutic nanomaterials have gained widespread attention as frontline materials for biomedical applications. The photoactivation strategies are classified as single-modality (based on either reactive oxygen species (ROS)-based photodynamic therapy (PDT), hyperthermia-based photothermal therapy (PTT)), or dual-modality (which combines PDT and PTT). Due to its minimal invasiveness, phototherapy has been extensively applied as an efficient therapeutic platform for many diseases, including skin cancers. However, extensive implementation of phototherapy to address the emergence of multidrug-resistant (MDR) bacterial infections remains challenging. This review focuses on copper sulfide (CuS) nanomaterials as efficient and cost-effective PDT and PTT therapeutic nanomaterials with antibacterial activity. The features and merits of CuS nanomaterials as therapeutics are compared to those of other nanomaterials. Control of the dimensions and morphological complexity of CuS nanomaterials through judicious synthesis is then introduced. Both the in vitro antibacterial activity and the in vivo therapeutic effect of CuS nanomaterials and derivative nanocomposites composed of 2D nanomaterials, polymers, metals, metal oxides, and proteins are described in detail. Finally, the perspective of photo-stimuli-responsive CuS nanomaterials for future clinical antibacterial applications is highlighted. This review illustrates that CuS nanomaterials are highly effective, low-toxic, and environmentally friendly antibacterial agents or platform nanomaterials for combatting MDR bacterial infections.

Recent advances in dual- and multi-responsive nanomedicines for precision cancer therapy.

Nanomedicines have been regarded as a potential approach in the field of cancer treatment due to their unique advantages. Although improved therapeutic efficacy can be achieved, the applications of most traditional nanomedicines are still limited by severe side effects resulting from unintended retention of therapeutic agents in non-diseased tissues. To increase the controllability of therapeutic agent accumulation in targeting sites (such as tumors), stimuli-responsive nanomedicines that realize drug release in response to exogenous or endogenous stimuli have been developed. In these stimuli-responsive nanomedicines, most of them are activated by mono type of stimulus, and therefore show unsatisfactory selectivity and specificity. In contrast, dual- and multi-responsive nanomedicines that integrate different responsive components into a signal nanoplatform can allow drug release in a more safe and effective manner, leading to both improved therapeutic efficacy and reduced systemic toxicity. Herein, we summarize recent advances in precision cancer therapy by using dual- and multi-responsive nanomedicines. The design strategies and working mechanisms of these dual- and multi-responsive nanomedicines and their applications in chemotherapy, phototherapy, and immunotherapy of cancer are introduced in detail. The existing challenges and future prospects are finally discussed in anticipation of accelerating the clinical translation of these nanomedicines.

Porous Silicon Carrier Endowed with Photothermal and Therapeutic Effects for Synergistic Wound Disinfection.

Drug carriers endowed with photothermal effects will allow the drug delivery system to release drugs in a thermal-stimuli manner. In addition, the photothermal therapy (PTT) will also interplay with therapeutic drugs loaded in the carrier to exhibit synergistic bioactivity for various disease treatment. However, endowing the drug carrier with photothermal and synergistic therapeutic effects still has challenge. Herein, we demonstrate that surface modification of porous silicon (PSi) with polydopamine (PDA) could endow the classical drug carrier with a significant photothermal effect for advanced antibacterial therapy and wound disinfection. Specifically, the PSi surface interacts with a Cu2+/PDA complex via a simple and fast surface reduction-induced deposition method, forming the unique CuPDA coated PSi microcarrier (CuPPSi) without blocking the mesoporous structure. The CuPPSi carrier generates a higher near-infrared (NIR) photothermal efficiency and improved drug loading capacity owing to the abundant functional groups of PDA. Stimuli-responsive release of antibacterial Cu2+ and loaded curcumin (Cur) from CuPPSi can be realized under multiple stimuli including pH, reactive oxygen species and NIR laser irradition. Benefited from the carrier's intrinsic multimodal therapy, the CuPPSi-Cur platform exhibits amplified, broad-spectrum, and synergistic antibacterial effect, killing more than 98% for both Staphylococcus aureus and Escherichia coli at a mild PTT temperature (∼45 °C). Notably, the combined therapy promotes migration of fibroblasts with no significant cytotoxicity as revealed through cell experiments in vitro. In bacteria-infected mice model, efficient bacterial ablation and wound healing are further demonstrated with negligible side effects in vivo. Overall, the rational design of a drug carrier with photothermal and therapeutic effects provides a novel intervention for amplifing wound disinfection clinically.

H2S responsive PEGylated poly (lipoic acid) with ciprofloxacin for targeted therapy of Salmonella.

Targeted antibiotic delivery system would be an ideal solution for the treatment of enteropathogenic infections since it avoids the excessive usage of antibiotics clinically, which may lead to threat on public health and food safety. Salmonella spp. are Enteropathogens, but they are also robust H2S producers in the intestinal tracts of hosts. To this end, the PEGylated poly (α lipoic acid) (PEG-PALA) copolymer nanoparticles with hydrophilic exterior and hydrophobic interior were designated in this study to encapsulate the antibiotics and release them in response to H2S produced by Salmonella spp. The PEG-PALA nanoparticles demonstrated excellent stability in vitro and biocompatibility toward mammalian Caco-2 and 293 T cells. The release of ciprofloxacin from PEG-PALA nanoparticle was only 25.44 ± 0.57% and 26.98 ± 1.93% (w/w) in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) solutions without H2S stimulation. However, the release amounts of ciprofloxacin were up to 73.68 ± 1.63% (w/w) in the presence of 1 mM Na2S as H2S source. In the mouse infection model, PEG-PALA nanoparticles encapsulated with ciprofloxacin (PEG-PALA@CIP) reduced the Salmonella colonization in the heart, liver, spleen, lung, cecum, and faeces, prolonged ciprofloxacin persistence in the intestine while reducing its absorption into the blood. More importantly, these nanoparticles reduced 3.4-fold of Enterobacteriaceae levels and increased 1.5-fold of the Lactobacillaceae levels compared with the drug administered in the free form. Moreover, these nanoparticles resulted in only minimal signs of intestinal tract inflammation. The H2S-responsive antibiotic delivery systems reported in this study demonstrating a variety of advantages including protected the drug from deactivation by gastric and intestinal fluids, maintained a high concentration in the intestinal tract and maximally kept the gut microbiota homeostasis. As such, this targeted antibiotic delivery systems are for the encapsulation of antibiotics to target specific enteropathogens.

Oxidation and Reduction Dual-Responsive Polymeric Prodrug Micelles Co-delivery Precisely Prescribed Paclitaxel and Honokiol for Laryngeal Carcinoma Combination Therapy.

Laryngeal carcinoma is the most common head and neck malignancy globally, and chemotherapy is still the most common treatment for this type of carcinoma. Monotherapy has become powerless because of the lack of drugs in the anticancer agent library, the difficult process of new drug discovery, and the widespread drug resistance. Combination therapy with two agents, in particular Chinese herbal medicines with chemotherapy drugs, is a potential alternative to chemotherapy alone. However, combination therapy faces difficulties in delivering multiple drugs to tumor tissue in a precise ratio. Here, a cocktail polymeric prodrug micelle (PHPPM) was developed using an oxidation and reduction dual-responsive polymeric paclitaxel (PTX) and polymeric honokiol (HK) prodrugs. Both of them were obtained by covalently conjugating the drug to dextran via diselenium bonds. Following optimization and characterization, the PHPPM with the precise mass ratio of PTX and HK was obtained, enabling ratiometric drug loading, synchronized drug release in response to tumor high-level reactive oxygen species and glutathione environment, long blood circulation, and high tumor accumulation. This co-delivery system can effectively inhibit laryngeal carcinoma growth in vitro and in vivo. Codelivery of chemotherapy agents and Chinese herbal medicine with a precise ratio and controlled release of the two drugs at the tumor site provides an effective approach to clinical therapy for other laryngeal carcinomas.

A multi-hit therapeutic nanoplatform for hepatocellular carcinoma: Dual stimuli-responsive drug release, dual-modal imaging, and in situ oxygen supply to enhance synergistic therapy.

Nanomedicine has been widely studied for the diagnosis and treatment of hepatocellular carcinoma (HCC). How to synthesize a nanoplatform possessing a high synergistic therapeutic efficacy remains a challenge in this emerging research field. In this study, a convenient all-in-one therapeutic nanoplatform (FTY720@AM/T7-TL) is designed for HCC. This advanced nanoplatform consists of multiple functional elements, including gold-manganese dioxide nanoparticles (AM), tetraphenylethylene (T), fingolimod (FTY720), hybrid-liposome (L), and T7 peptides (T7). The nanoplatform is negatively charged at physiological pH and can transit to a positively charged state once moving to acidic pH environments. The specially designed pH-responsive charge-reversal nanocarrier prolongs the half-life of nanodrugs in blood and improves cellular uptake efficiency. The platform achieves a sustained and controllable drug release through dual stimulus-response, with pH as the endogenous stimulus and near-infrared as the exogenous stimulus. Furthermore, the nanoplatform realizes in situ O2 generation by catalyzing tumor over-expressed H2O2, which alleviates tumor microenvironment hypoxia and improves photodynamic therapy. Both in vitro and in vivo studies show the prepared nanoplatform has good photothermal conversion, cellular uptake efficiency, fluorescence/magnetic resonance imaging capabilities, and synergistic anti-tumor effects. These results suggest that the prepared all-in-one nanoplatform has great potential for dual-modal imaging-guided synergistic therapy of HCC.