On-demand Drug Release Research Articles

Ultrasound-triggered nano delivery of lenvatinib for selective immunotherapy treatment against hepatocellular carcinoma

Although there have been remarkable advances in the treatment of hepatocellular carcinoma (HCC), the prognosis remains poor in those with advanced stage and more effective therapeutic options are urgently needed. Lenvatinib (Len), a multiple receptor tyrosine kinase inhibitor, is an emerging molecular targeted agent for HCC, whose immunomodulatory activities have been investigated. However, Len utilization is limited because of its low metabolic stability, poor bioavailability and dose-dependent toxicity, rendering its direct use insufficient for immune modulation. Stimuli-responsive nanoparticles, which are drug-targeted delivery platforms for on-demand drug release, facilitate deeper and uniform tumour penetration, providing alternative solutions to overcome current limitations. Ultrasound (US) exhibits superior tissue penetration abilities and can produce reactive oxygen species (ROS) at the tumour site to treat deeper tumours. In addition, US serves as an excellent and selective drug delivery mediator for tumour treatment. Herein, we designed US-triggered lenvatinib nanoparticles (Len-RNPs) for selective drug delivery that utilize US-triggered ROS to induce in situ oxidation reactions, resulting in nanoparticle disintegration. Len-RNPs mitigate the toxicity of Len and effectively trigger robust systemic anti-tumour immune responses in a H22 tumour model, resulting in a tumour suppression rate of 95.7%, with 60% of mice being cured. Our study elucidates a novel and precise strategy of combining Len and US therapy for enhanced HCC immunotherapy.

Modular Assembly of Photoactive Lipid Nanoparticles on Red Blood Cells toward Enhanced Phototherapy Efficacy.

Photodynamic therapy has been developed as a promising treatment for malignant tumors, which inspires research into photosensitizers. However, the therapeutic efficacy of individual photosensitizers is often hampered by the physiological environment. The assembly of biological materials with synthetic molecules offers a strategy to enhance functionality while improving tolerance to varying physiological conditions. Herein, we present a biohybrid system for enhanced phototherapy efficacy through a simple two-step assembly process. Photoactive lipid nanoparticles were assembled based on synthesized conjugated molecules and lipophilic prodrugs, which were then modularly assembled with red blood cells (RBCs). Driven by hydrophobic and electrostatic interactions, hydrophobic conjugated molecules were efficiently incorporated into the RBCs, while lipophilic prodrugs were simultaneously inserted into the cell membranes. The engineered RBCs harnessed the natural oxygen transport capability, enabling the internal conjugated molecules to effectively produce reactive oxygen species (ROSs) even under oxygen-poor conditions. Meanwhile, the use of ROS-cleavable linkers in prodrugs enhanced drug release for chemotherapy, which is a perfect complement to photodynamic therapy. In vitro and in vivo experiments proved the improved phototherapy efficacy of the biohybrid system. Furthermore, the changes in aggregation directed Förster resonance energy transfer between conjugated molecules and fluorescent drugs provided a mechanism to track drug release from engineered RBCs. Therefore, the modular assembly of biohybrid systems can offer multiple functionalities required for phototherapy, on-demand drug release, and imaging.

Drug Release via Ultrasound-Activated Nanocarriers for Cancer Treatment: A Review

Conventional cancer chemotherapy often struggles with safely and effectively delivering anticancer therapeutics to target tissues, frequently leading to dose-limiting toxicity and suboptimal therapeutic outcomes. This has created a need for novel therapies that offer greater efficacy, enhanced safety, and improved toxicological profiles. Nanocarriers are nanosized particles specifically designed to enhance the selectivity and effectiveness of chemotherapy drugs while reducing their toxicity. A subset of drug delivery systems utilizes stimuli-responsive nanocarriers, which enable on-demand drug release, prevent premature release, and offer spatial and temporal control over drug delivery. These stimuli can be internal (such as pH and enzymes) or external (such as ultrasound, magnetic fields, and light). This review focuses on the mechanics of ultrasound-induced drug delivery and the various nanocarriers used in conjunction with ultrasound. It will also provide a comprehensive overview of key aspects related to ultrasound-induced drug delivery, including ultrasound parameters and the biological effects of ultrasound waves.

Injectable and pH-Responsive Metformin-Loaded Hydrogel for Active Inhibition of Posterior Capsular Opacification.

Posterior capsular opacification (PCO) is a common complication following cataract surgery, which can lead to a significant vision loss. This study introduces a facile method for developing a metformin-derived hydrogel (HCM6) stabilized by dynamic covalent bonds among natural polymers. This hydrogel demonstrates antifibrotic properties, on-demand drug release, pH responsiveness, injectability, and self-healing capabilities. Our in vitro experiments confirmed that the HCM6 hydrogel exhibits excellent biocompatibility, inhibiting lens epithelial cell migration, and transforming growth factor-2β (TGFβ2)-induced α-smooth muscle actin (α-SMA) expression in lens epithelial cells. In vivo studies conducted in a rat extracapsular lens extraction (ECLE) model revealed that HCM6 significantly suppressed PCO after 21 days of implantation with no observed pathological effects on surrounding tissues or the optic nerve. According to our experimental results, the inhibitory mechanism of PCO may be attributed to metformin's suppressive effect on lens cell migration, epithelial-mesenchymal transition (EMT), and lens fiber formation. In summary, the long-acting, controllable, and on-demand release characteristics of the HCM6 hydrogel not only provide an effective strategy for preventing PCO but also offer new avenues for treating undesirable proliferative conditions in ophthalmology and beyond.

Recent Advancement of Novel Drug Delivery Systems for Topical Anaesthesia Formulations

Abstract: In recent years, there have been exciting developments in improving how we deliver anaesthesia through the skin. Nanotechnology is a key player, using tiny particles to encapsulate and transport anaesthetic agents, ensuring a controlled and steady release. This helps overcome challenges like inconsistent absorption and short-lasting effects seen with traditional methods. Transdermal patches are gaining attention too; they release drugs slowly and steadily, eliminating the need for frequent reapplication while maintaining a constant drug level at the application site. Smart polymers are bringing innovation by responding to specific triggers, enabling on-demand drug release. This allows for personalized anaesthesia based on individual patient needs. In recent years, there have been exciting developments in improving how we deliver anaesthesia through the skin. Nanotechnology is a key player, using tiny particles to encapsulate and transport anaesthesia agents, ensuring a controlled and steady release. This helps overcome challenges like inconsistent absorption and other short-lasting effects seen with traditional methods. Microemulsion systems, made of water, oil, surfactants, and co-surfactants, are another promising approach. They enhance drug solubility and availability, providing a stable environment for including anaesthesia agents. Transdermal patches are gaining attention too; they release drugs slowly and steadily, eliminating the need for frequent reapplication and maintaining a constant drug level at the application site. Smart polymers are bringing innovation by responding to specific triggers, enabling on-demand drug release. This allows for personalized anaesthesia based on individual patient needs. Together, these advancements mark a significant shift towards more effective, patient-friendly, and personalized topical anaesthesia delivery systems.

Ultrasound-Induced Release Profile of Nimodipine from Drug-Loaded Block Copolymers after Singular vs. Repeated Sonication: In Vitro Analysis in Artificial Cerebrospinal Fluid.

Nimodipine still represents a unique selling point in the prevention of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH). Its intrathecal effect is limited by a low oral bioavailability, leading to the development of nanocarrier systems to overcome this limitation. This study investigated the ultrasound-induced release profile of nimodipine from drug-loaded copolymers in artificial cerebrospinal fluid (CSF) within 72 h after a singular versus repeated sonication. Pluronic® F127 copolymers (Sigma-Aldrich, Taufkirchen, Germany)were loaded with nimodipine by direct dissolution. Spontaneous and on-demand drug release by ultrasound (1 MHz at 1.7 W/cm2) was determined in artificial cerebrospinal fluid using the dialysis bag method. Nimodipine concentrations were measured at predefined time points within 72 h of sonication. Spontaneous release of nimodipine was enhanced by ultrasound application with significantly increased nimodipine concentrations two hours after a repeated sonication compared to a singular sonication (median 1.62 vs. 17.48 µg/µL, p = 0.04). A further trend was observed after four hours (median 1.82 vs. 22.09 µg/µL, p = 0.06). There was no difference in the overall nimodipine concentrations between the groups with a singular versus repeated sonication (357.2 vs. 540.3 µg/µL, p = 0.60) after 72 h. Repeated sonication resulted in an acceleration of nimodipine release from the drug-loaded copolymer in a CSF medium. These findings confirm the proof of principle of an on-demand guidance of nimodipine release from nimodipine-loaded nanodrugs by means of ultrasound, which suggests that evaluating the concept in an animal model may be appropriate.

3D-Printed Phenylboronic Acid-Bearing Hydrogels for Glucose-Triggered Drug Release.

Diabetes is a major health concern that the next-generation of on-demand insulin releasing implants may overcome via personalized therapy. Therein, 3D-printed phenylboronic acid-containing implants with on-demand glucose-triggered drug release abilities are produced using high resolution stereolithography technology. To that end, the methacrylation of phenylboronic acid is targeted following a two-step reaction. The resulting photocurable phenylboronic acid derivative is accordingly incorporated within bioinert polyhydroxyethyl methacrylate-based hydrogels at varying loadings. The end result is a sub-centimeter scaled 3D-printed bioinert implant that can be remotely activated with 1,2-diols and 1,3-diols such as glucose for on-demand drug administration such as insulin. As a proof of concept, varying glucose concentration from hypoglycemic to hyperglycemic levels readily allow the release of pinacol, i.e., a 1,2-diol-containing model molecule, at respectively low and high rates. In addition, the results demonstrated that adjusting the geometry and size of the 3D-printed part is a simple and suitable method for tailoring the release behavior and dosage.

Implantable and wireless-controlled antibacterial patch for deep abscess eradication and therapeutic efficacy monitoring

Pyogenic abscesses in deep organs represent severe bacterial infections that can be life-threatening. Traditional sonodynamic and photodynamic hybrid therapy (SDT/PDT) faces various limitations when treating deep organ abscess, including difficulties in drug release control, limited penetration of external laser, a hypoxic microenvironment, and challenges in therapeutic efficacy monitoring. To address these issues, we develope an implantable and wireless-controlled antibacterial patch integrated with modules for on-demand drug release, light control and therapeutic efficacy monitoring, providing a comprehensive solution to the clinical challenges of PDT/SDT in treating deep organ abscess. This self-adhesive and miniaturized patch can easily attach to internal tissues, and be wirelessly powered and controlled by external ultrasound. Initially, ultrasound powers the patch’s drug release module through the lead zirconate titanate piezoelectric transducer (PZT), providing distinct electrical-thermal release signals for indocyanine green (ICG) and hemoglobin (Hb). This ensures that Hb is released first to generate oxygen, alleviating the hypoxic microenvironment at the infection site, followed by the release of ICG as both a photosensitizer and sonosensitizer. Subsequently, ultrasound directly activates the sonosensitizer and powers the µLEDs in the light control module, ultimately initiating SDT/PDT hybrid antibacterial treatment. The therapeutic efficacy monitoring module in the patch uses hydrogels with infection detection capabilities to provide timely feedback on the treatment status of the infected lesions, enabling doctors to rapidly adjust treatment plans and significantly improve the flexibility and effectiveness of treatments. Both in vitro and in vivo experiments demonstrate that the patch can completely cure pyogenic liver abscesses. This research also exhibits promise for extending the application of the patch to treat other types of deep infections.

Red Blood Cell Membrane Spontaneously Coated Nanoprodrug Based on Phosphatidylserine for Antiatherosclerosis Applications.

Atherosclerosis (AS) is characterized by the accumulation of lipids within the walls of coronary arteries, leading to arterial narrowing and hardening. It serves as the primary etiology and pathological basis for cardiovascular diseases affecting the heart and brain. However, conventional pharmacotherapy is constrained by inadequate drug delivery and pronounced toxic side effects. Moreover, the inefficacy of nanomedicine delivery systems in controlling disease progression may be attributed to nonspecific clearance by the mononuclear phagocyte system. Thus, a biomimetic platform spontaneously enveloped by red blood cell membrane is exploited for anti-atherosclerosis applications, offering favorable biocompatibility. The CLIKKPF polypeptide is introduced to develop red blood cell membrane spontaneously encapsulated nanotherapeutics only through simple coincubation. Given the functional modifications, RBC@P-LVTNPs is beneficial to facilitate the target drug delivery to the atherosclerotic lesion, responding precisely to the pathological ROS accumulation, thereby accelerating the on-demand drug release. Both in vivo and in vitro results also confirm the significant therapeutic efficacy and favorable biocompatibility of the biomimetic nanomedicine delivery system, thus providing a promising candidate for nanotherapeutics against AS.

Biomedical applications of stimuli-responsive nanomaterials.

Nanomaterials have aroused great interests in drug delivery due to their nanoscale structure, facile modifiability, and multifunctional physicochemical properties. Currently, stimuli-responsive nanomaterials that can respond to endogenous or exogenous stimulus display strong potentials in biomedical applications. In comparison with conventional nanomaterials, stimuli-responsive nanomaterials can improve therapeutic efficiency and reduce the toxicity of drugs toward normal tissues through specific targeting and on-demand drug release at pathological sites. In this review, we summarize the responsive mechanism of a variety of stimulus, including pH, redox, and enzymes within pathological microenvironment, as well as exogenous stimulus such as thermal effect, magnetic field, light, and ultrasound. After that, biomedical applications (e.g., drug delivery, imaging, and theranostics) of stimuli-responsive nanomaterials in a diverse array of common diseases, including cardiovascular diseases, cancer, neurological disorders, inflammation, and bacterial infection, are presented and discussed. Finally, the remaining challenges and outlooks of future research directions for the biomedical applications of stimuli-responsive nanomaterials are also discussed. We hope that this review can provide valuable guidance for developing stimuli-responsive nanomaterials and accelerate their biomedical applications in diseases diagnosis and treatment.

Smart wireless flexible bandage containing drug loaded polycaprolactone microparticles for real-time monitoring and treatment of chronic wounds.

The quality of life is negatively impacted by chronic wounds for more than 25 million people in the US. They are quite prone to infection, which may lead to the eventual loss of a limb. By exposing the ulcers to treatment agents at the appropriate time, the healing rate is increased. On-demand drug release in a closed-loop system will aid us in reaching our goal. In this study, we have developed a platform capable of real-time diagnosis of bacterial infection by wirelessly reading wound pH, as well as slow and on-demand local administration of antibiotics. The drug carrier microparticles, an electrical patch, a thermoresponsive hydrogel with an integrated microheater, and a flexible pH sensor comprised the closed-loop patch. Here it is reported that slow and smart release of cefazolin can be addressed by incorporation of drug encapsulated hydrophobic microparticles embedded into a thermo-responsive hydrogel. The utilization of a programmable bandage to provide antibiotic medication highlights the need of not only choosing appropriate therapeutic substances but also the controlled release of the medicine and its rate of release within the wound area. The results of our study indicate that the use of cefazolin encapsulated polycaprolactone (PCL) microparticles can effectively regulate the application of antibiotic treatment for chronic skin wounds. The results also showed a substantial gradual release of cefazolin from the thermo-responsive Pnipam hydrogel when the wound dressing was subjected to a temperature of 37°C. We believe that the developed flexible smart bandage can have a significant impact on chronic wound healing.

Diselenide-Bridged Mesoporous Silica-Based Nanoplatform with a Triple ROS-Scavenging Effect for Intracerebral Hemorrhage Treatment.

Oxidative stress (OS) is a major mediator of secondary brain injury following intracerebral hemorrhage (ICH). Thus, antioxidant therapy is emerging as an attractive strategy to combat ICH. To achieve both reactive oxygen species (ROS) scavenging ability and on-demand drug release ability, we constructed a novel polydopamine (PDA)-coated diselenide-bridged mesoporous silica nanoparticle (DSeMSN) drug delivery system (PDA-DSeMSN). Edaravone (Eda) was blocked in the pores of DSeMSN by covering the pores with PDA as a gatekeeper. The drug maintained nearly "zero release" before reaching the lesion site, while in the ROS-enriched circumstances, the PDA shell went through degradation and the doped diselenide bonds broke up, triggering the disintegration of nanoparticles and leading to Eda release. Interestingly, the ROS-degradable property of the PDA shell and diselenide bond endowed the system with enhanced ROS-eliminating capacity. The synergistic effect of ROS-responsive drug delivery and ROS-scavenging PDA-DSeMSN showed efficient antioxidative and mitochondria protective performance without apparent toxicity in vitro. Importantly, PDA-DSeMSN@Eda through intravenous administration specifically accumulated in perihematomal sites and demonstrated robust neuroprotection in an ICH mouse model through antioxidative and antiapoptotic effects with high biological safety. Thus, the PDA-DSeMSN platform holds tremendous potential as an excellent carrier for on-demand delivery of drugs and provides a new and effective strategy for the clinical treatment of ICH.

Core-crosslinked polyprodrug nanoparticles via facile crosslinking-induced self-assembly for tumor intracellular acid-triggered doxorubicin delivery

Premature drug leakage from the drug delivery systems (DDSs) causes severe toxic side effects on the normal cells, restricting their practical application in tumor chemotherapy. Here, core-crosslinked polyprodrug nanoparticles were designed by facile crosslinking-induced self-assembly of polyethylene glycol-b-poly(p-formylphenyl methacrylate) (PEG-PFPMA) di-block copolymer via acid-labile Schiff base bonds, with a pH-responsive doxorubicin-doxorubicin dimer (Di-DOX-ADH) as crosslinker. Owing to the unique structure, the chemotherapeutic drug, doxorubicin (DOX), could be released only when the Schiff base bond and hydrazone bond on both sides of the DOX unit were cleaved. Thus, a leakage-free tumor intracellular acid-triggered on-demand drug release was achieved with cumulative DOX release of 80 % in the simulated tumor intracellular microenvironment in 80 h. The proposed core-crosslinked polyprodrug nanoparticles could be internalized by the HepG2 cells and released DOX therein, exhibiting an enhanced tumor growth inhibition than free DOX.

Micelle-Containing Hydrogels and Their Applications in Biomedical Research.

Hydrogels are one of the most commonly used materials in our daily lives, which possess crosslinked three-dimensional network structures and are capable of absorbing large amounts of fluid. Due to their outstanding properties, such as flexibility, tunability, and biocompatibility, hydrogels have been widely employed in biomedical research and clinics, especially in on-demand drug release. However, traditional hydrogels face various limitations, e.g., the delivery of hydrophobic drugs due to their highly hydrophilic interior environment. Therefore, micelle-containing hydrogels have been designed and developed, which possess both hydrophilic and hydrophobic microenvironments and enable the storage of diverse cargos. Based on the functionalities of micelles, these hydrogels can be classified into micelle-doped and chemically/physically crosslinked types, which were reported to be responsive to varied stimuli, including temperature, pH, irradiation, electrical signal, magnetic field, etc. Here, we summarize the research advances of micelle-containing hydrogels and provide perspectives on their applications in the biomedical field based on the recent studies from our own lab and others.

Tailoring lyotropic liquid crystals for skin barrier penetration: Exploring composition and structure–function relationships

Lyotropic liquid crystals (LLCs) have garnered attention as a promising nanocarrier delivery system for enhancing skin permeation owing to their unique structural properties, such as improved drug loading and controlled drug release and versatility. LLCs are greatly explored for topical drug delivery owing to their strong bio-adhesive nature and structural similarity to the biological membranes when applied topically, which improves skin retention and permeation of the drugs. This review explores the functionality of structural design, especially the optimization of micellar systems, hexagonal and lamellar phases, and bicontinuous cubic and sponge phases, to achieve efficient skin permeation of therapeutic loaded LLCs. Furthermore, customization of surfactant to achieve skin compatibility and permeation is explored along with incorporating molecular modifications, functionalization, and the influence of surfactant hydrophilic–lipophilic balance. Additionally, the review illuminates the impact of LLCs curvature and the engineering of ordered and disordered phases for optimal drug release. Emerging advanced techniques such as surface modification with various ligands, stimuli-responsive LLCs for on-demand drug release, and combination therapies with multifunctional LLCs for synergistic effects that can promote targeted and site-specific drug delivery have also been discussed. The detailed findings have been discussed in this review with appropriate case studies. Challenges and future perspectives in designing and formulating LLCs for skin permeation are addressed to ignite future research. The knowledge and advancements presented in this review pave the way for developing next-generation LLCs-based systems, enabling enhanced permeation through the skin and opening new possibilities in the treatment of various dermatological conditions.

Photothermal responsive porous hollow microneedles as Chinese medicine versatile delivery system for wound healing.

Chinese medicine is identified as a candidate for wound healing. Attempts in this field tend to develop efficient dosage forms for delivering Chinese medicine with low side effects. In this paper, we proposed novel photothermal responsive porous hollow microneedles (PRPH-MNs) as a versatile Chinese medicine delivery system for efficient antibacterial wound treatment. The PRPH-MNs are composed of porous resin shells with good mechanical property, hydrogel cores, and a photothermal graphene oxide hybrid substrate. The hollow structure provides sufficient space for loading the drug dispersed hydrogel, while the porous resin shells could not only block the direct contact between drugs and wound sites but also provide channels for facilitating the drug release from the core. In addition, benefiting from the photothermal effect of their substrate, the PRPH-MNs could be heated under near-infrared (NIR) irradiation for controllable promotion of drug release. Based on these features, we have proved that the antibacterial Chinese medicine Rhein loaded PRPH-MNs were effective in promoting wound healing due to their good antibacterial property and on-demand drug release. Thus, we believe that the proposed PRPH-MNs are valuable for delivery of different drugs for clinical applications.

Tunicate cellulose nanocrystals strengthened injectable stretchable hydrogel as multi-responsive enhanced antibacterial wound dressing for promoting diabetic wound healing

The intricate microenvironment of diabetic wounds characterized by hyperglycemia, intense oxidative stress, persistent bacterial infection and complex pH fluctuations hinders the healing process. Herein, an injectable multifunctional hydrogel (QPTx) was developed, which exhibited excellent mechanical performance and triple responsiveness to pH, temperature, and glucose due to dynamic covalent cross-linking involving dynamic Schiff base bonds and phenylboronate esters with phenylboronic-modified quaternized chitosan (QCS-PBA), polydopamine coated tunicate cellulose crystals (PDAn@TCNCs) and polyvinyl alcohol (PVA). Furthermore, the hydrogels can incorporate insulin (INS) drugs to adapt to the complex and variable wound environment in diabetic patients for on-demand drug release that promote diabetic wound healing. Based on various excellent properties of the colloidal materials, the hydrogels were evaluated for self-healing, rheological and mechanical properties, in vitro insulin response to pH/temperature/glucose release, antibacterial, antioxidant, tissue adhesion, coagulation, hemostasis in vivo and in vitro, and biocompatibility and biodegradability. By introducing PDAn@TCNCs particles, the hydrogel has photothermal antibacterial activity, enhanced adhesion and oxidation resistance. We further demonstrated that these hydrogel dressings significantly improved the healing process compared to commercial dressings (Tegaderm™) in full-layer skin defect models. All indicated that the glucose-responsive QPTx hydrogel platform has great potential for treating diabetic wounds.

Baicalein loaded liposome with hyaluronic acid and Polyhexamethylene guanidine modification for anti methicillin-resistant Staphylococcus aureus infection

Targeting delivery to the infection site and good affinity of vehicle to the bacterial are two main concerns in therapy of bacterial infection, and on-demand release of drug is another important issue. In this work, a liposome drug delivery system (HA/P/BAI-lip) incorporated with baicalein and modified by PHMG and HA was prepared. Several characterizations were conducted to examine the physical properties of liposome. Then it was applied to treatments of MRSA induced dorsal subcutaneous abscess model and the thigh muscle infected model. The presence of guanidine group in HA/P/BAI-lip rendered the liposome satisfactory bacterial target ability and good pH sensitive properties. The lipase secreted by bacterial could promote the hydrolysis of soybean phosphatidylcholine (SPC) in liposome. The modification of HA in HA/P/BAI-lip could lead the drug system to the exact infected site where CD44 was abundant because of inflammation. The low pH microenvironment characteristic of bacterial infection could induce the swelling of liposome following by degradation. Taken together, baicalein could be released selectively at the infected site to exert antibacterial capacity. HA/P/BAI-lip showed impressive antibacterial ability and dramatically decrease the bacterial burden of infection site and alleviate the infiltration of inflammatory cells, facilitating the recovery of infection.

Lipo/TK-CDN/TPP/Y6 nanoparticles inhibit cutaneous melanoma formation

Stimulation of the innate immune stimulator of interferon genes (STING) pathway has been shown to boost anti-tumour immunity. Nevertheless, the systemic delivery of STING agonists to the tumour presents challenges. Therefore, we designed a cyclic dinucleotide (CDN)-based drug delivery system (DDS) combined photothermal therapy (PTT)/photodynamic therapy (PDT)/immunotherapy for cutaneous melanoma. We coencapsulated a reactive oxygen species (ROS)-responsive prodrug thioketone-linked CDN (TK-CDN), and photoresponsive agents chlorin E6 (Y6) within mitochondria-targeting reagent triphenylphosphonium (TPP)-modified liposomes (Lipo/TK-CDN/TPP/Y6). Lipo/TK-CDN/TPP/Y6 exhibited a photothermal effect similar to Y6, along with a superior cellular uptake rate. Upon endocytosis by B16F10 cells, Lipo/TK-CDN/TPP/Y6 generated large amounts of ROS under laser irradiation for PDT. Mice bearing B16F10 tumours were intravenously injected with Lipo/TK-CDN/TPP/Y6 and exposed to irradiation, resulting in a substantial inhibition of tumour growth. Exploration of the mechanism of anti-tumour action showed that Lipo/TK-CDN/TPP/Y6 had a stronger stimulation of STING activation and anti-tumour immune cell infiltration compared to other groups. Hence, the Lipo/TK-CDN/TPP/Y6 nanoparticles offer great potential as a DDS for targeted and on-demand drug release at tumour sites. These nanoparticles exhibit promise as a candidate for precise and controllable combination therapy in the treatment of tumours.

Photoresponsive silver nanowire nanoplatform for real-time drug delivery in non-small cell lung cancer therapy

In this study, we first successfully synthesized three different sizes and shapes of Ag nanowires (Ag NWs) using a polyol synthesis method. The size and morphology of the Ag NWs were controlled by the types of inorganic control agents in the reaction system (NaCl for 1, CuCl2 for 2, and FeCl3 for 3). The synthesized Ag NWs were characterized using scanning electron microscopy (SEM) and powder X-ray diffraction (PXRD) experiments. Subsequently, due to the favorable width of 1, we utilized it as an effective photosensitizer to construct a novel drug-loaded nanomaterial platform, namely 1-PLC@DOX (PLC stands for poly(ε-caprolactone), and DOX stands for Doxorubicin), to achieve on-demand drug release triggered by near-infrared (NIR) laser. The results indicate that the drug delivery system can achieve minimally invasive treatment of complex geometric defects. Under near-infrared irradiation, 1-PLC@DOX can heat up to 53.6 °C within 15 min, showing a unique heating platform on the heating curve, with ideal photothermal stability and heating effect compared to other groups. By toggling near-infrared irradiation on or off, 1-PLC@DOX can exhibit a stair-step drug release curve, suggesting that on-demand control of drug release using near-infrared laser as a trigger is feasible. In vitro biological evaluations demonstrate that 1-PLC@DOX exhibits good biocompatibility and anti-tumor ability, significantly reducing the invasive ability of A549 cells on non-small cell lung cancer (NSCLC) cells, and at the same time inhibiting the proliferation of cancer cells by regulating the p53 signaling pathway to cause apoptosis.