Construction and evaluation of a long-circulating thermosensitive liposomal black phosphorus quantum dot delivery system for osteosarcoma therapy.

The effect of hyperthermic cycling on intratumoral liposome accumulation and triggered drug release.

Polyglutamic acid and Pluronic F127-based hydrogel for loading sinomenine hydrochloride liposomes in the treatment of rheumatoid arthritis.

Thermosensitive hydrogel containing liposomal nanoparticles of deferoxamine and curcumin: In vitro evaluation and diabetic wound healing effect in rats.

Unveiling human brain tumor response to tumor treating fields mediated thermosensitive liposome drug delivery: A heat and mass transfer optimization

Ocular malignancies provide a unique therapeutic challenge because of their anatomical intricacy, limited accessibility, and vision-critical nature. Recent developments in radiopharmaceutical design have been paired with ultrasound-mediated medicine administration to create highly targeted, less invasive therapies for intraocular cancers. This research looks at the emerging topic of ultrasound-responsive radiopharmaceutical devices built specifically for ocular oncology. These methods enhance tumor selectivity, decrease off-target effects, and enable real-time imaging-guided therapy by utilizing targeted ultrasound to induce localized medication release or radiotherapeutic agent activation. Microbubble-assisted delivery, thermosensitive liposomes, and phase-transition nanodroplets carrying radionuclides have all been designed to optimize ocular pharmacokinetics and tissue penetration. Preclinical studies reveal promising results in increasing radiotherapeutic efficacy against retinoblastoma and uveal melanoma while sparing healthy ocular tissues.

Diffusion Coefficients of Surface Modified Liposomes and Thermo-sensitive Liposomes Measured by Optoelectronically Induced Transient Grating Method

Chemotherapeutic agents are widely used in cancer treatment but often induce severe off-target toxicity due to their nonspecific distribution. To address this limitation, we developed an innovative mesenchymal stem cell-based drug delivery system incorporating doxorubicin encapsulated in CO2-bubble-generating thermosensitive liposomes (MSC-DOX-BG-LPs) for controlled and tumor-targeted DOX release under near-infrared (NIR) irradiation. MSCs inherently migrate to tumor tissues via CXCR4-CXCL12 chemotactic signaling, enabling precise tumor targeting. MSC-DOX-BG-LPs remain stable during systemic circulation and regulate DOX release in response to heat-induced liposomal destabilization and CO2 bubble formation, ensuring localized drug activation while minimizing systemic side effects. In vitro and in vivo experiments demonstrated that MSC-DOX-BG-LPs, upon NIR irradiation, effectively inhibited tumor proliferation and angiogenesis while inducing apoptosis in tumor cells (***P < 0.001). Importantly, MSC-mediated delivery significantly enhanced drug accumulation within the tumor microenvironment, overcoming limitations associated with passive liposomal carrier delivery. These findings highlight MSC-DOX-BG-LPs as a promising platform for targeted chemotherapy that integrates tumor-specific migration with externally controlled drug release. This approach has the potential to improve therapeutic outcomes and prolong the survival of patients with various solid tumors.

Peptide‐based therapeutic strategies offer considerable potential for tumor immunotherapy but suffer from poor systemic bioavailability, rapid plasma clearance, and limited tumor‐targeting efficiency. To address these challenges, a biomimetic, photothermal‐responsive liposomal delivery system was developed that enables precise delivery of immunotherapeutic peptides while enhancing the synergistic effects of photothermal therapy. This system enhances peptide stability through fluorination, disrupts post‐translational modifications of PD‐L1, and promotes its degradation, thereby amplifying the anti‐tumor immune response. The carrier core consisted of thermosensitive 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphocholine (DPPC) liposomes loaded with the low‐toxicity photosensitizer indocyanine green (ICG), which facilitated controlled peptide release via the photothermal effect. Simultaneously, mild photothermal stimulation induced immunogenic cell death (ICD), further strengthening anti‐tumor immunity. To enhance tumor targeting, extend systemic circulation time, and improve drug accumulation at tumor sites, the carrier surface was coated with a platelet membrane, which increased biocompatibility and promoted immune evasion. Notably, in vivo studies demonstrated that the developed bioengineering platform significantly suppressed tumor growth in both solid and diffuse malignant tumors while inducing persistent immune memory, thereby facilitating long‐term anti‐tumor immune responses. Collectively, this approach establishes a novel framework for integrating peptide drug delivery with photothermal therapy, offering a promising strategy for advancing tumor immunotherapy.

Local drug delivery of irinotecan with phosphatidyldiglycerol-based thermosensitive liposomes reduces systemic exposure and increases therapeutic efficacy compared to systemic drug and Onivyde®.

Drug release from liposomes loaded by remote loading can proceed via two principal routes: (i) the leakage of the entrapped drug through membrane pores; (ii) the permeation of the drug through the intact membrane as the gradient used for remote loading is collapsed ("unloading"). We assess the contributions of the two release mechanisms for doxorubicin loaded via a pH-gradient into lysolipid-containing thermosensitive liposomes. To this end, release into buffer at physiological pH is compared with release into acidic buffer which should eliminate unloading but leave leakage largely unaffected. Above the transition point at ≈41 °C, unloading contributes ∼30% to the overall fast drug release occurring within 30 s. Immediately below the transition, there is still partial release and partial collapse of the pH-gradient but no substantial unloading. This can be explained by a low permeability of gel-phase lipid for (even deprotonated) doxorubicin and insufficient deprotonation at these pH values.

We encapsulate versatile photosensitizer (PS) IR-MnO2, prepared by binding a photothermal agent/PS IR820 to bovine serum albumin-MnO2 (BSA-MnO2), in the core of thermosensitive liposomes. The IR-MnO2 can enhance the efficacy of photodynamic therapy induced by near-infrared (NIR) light by generating oxygen in the acidic tumor microenvironment. Quercetin (Q) was coencapsulated in lipid bilayers to prepare IRQL, which can release IR-MnO2 and quercetin in response to NIR light. Quercetin can enhance the efficacy of photothermal therapy by sensitizing cancer cells to thermal stress from heat shock protein 70 (HSP70) downregulation, which simultaneously serves as an anticancer agent for chemotherapy. The loading efficiencies of IR-MnO2 and quercetin in the ∼160 nm IRQL are 83.1% and 65.5%, respectively. For targeted cancer therapy, a cell-penetrating peptide (CPP) was conjugated to IRQL to produce IRQL/CPP with an ∼180 nm size. In vitro studies show enhanced intracellular uptake of IRQL/CPP by U87 glioblastoma cells, which provides a photoenhanced nanoplatform for photochemo combination cancer therapy. Intravenous delivery of IRQL/CPP plus NIR laser irradiation to tumor-bearing nude mice using subcutaneously implanted U87 cells can significantly prevent tumor growth from bioluminescence intensity and tumor volume measurements and extend the animal survival time without biological side effects.

This study explores the optimization of hyperthermia-mediated drug delivery using thermo-sensitive liposomes (TSLs) for treating hepatocellular carcinoma (HCC). By employing a Multi-Objective Genetic Algorithm (MOGA), the research aims to maximize tumor cell kill rates while minimizing thermal damage to tissues. The mathematical models used include the Pennes' bioheat equation and drug diffusion equations, integrated into finite element simulations. The optimization process balances critical parameters which drive both heating protocol and drug release mechanisms, resulting in improved therapeutic outcomes. This innovative approach addresses the challenges of effective TSL-mediated chemotherapy, providing a promising pathway for enhancing clinical treatments of HCC.Clinical Relevance- This study is significant for clinicians as it proposes a computational method to obtain optimized input protocols for hyperthermia-mediated drug delivery in HCC. By fine-tuning treatment parameters, the approach aims to increase drug efficacy while reducing side effects, offering a more targeted and efficient alternative to conventional chemotherapy.

In hepatocellular carcinoma ablation, unclear tumor boundaries and localization often lead to incomplete treatment. Traditional iodinated contrast agents, although effective in distinguishing tumors, have rapid metabolism, limiting sustained visualization during ablation. Iodixanol-loaded thermosensitive liposomes were prepared by using the thin-film hydration method. Their temperature-responsive properties and CT imaging performance were validated through in vitro experiments, while in vivo studies were conducted to evaluate their CT imaging efficacy and potential as an auxiliary imaging agent in ablation therapy. This study successfully created stable, iodixanol-loaded thermosensitive liposomes that effectively outline HCC boundaries and accurately show the ablation zone during treatment. Iodixanol-loaded thermosensitive liposomes enable precise localization of ablation margins, facilitating more accurate clinical assessment of therapeutic outcomes and treatment end points.

This study aimed to prepare mitoxantrone thermosensitive liposome (MTX-TSL) to enhance the targeting capability of liposomes and thus improve the therapeutic effect of the drug on prostate cancer. MTX-TSL were prepared using the thin-film hydration method. A single-factor experiment was conducted to optimize the formulation process, and the liposome quality was assessed alongside short-term stability testing. The in vitro efficacy of MTX-TSL was evaluated using RM-1 prostate cancer cell inhibition assays. In vivo experiments were conducted on BDF1 mice inoculated with RM-1 cells to assess the tissue distribution and anticancer activity of MTX-TSL. Quality assessments of MTX-TSL revealed a pH of 6.53 ± 0.02, osmotic pressure of 309 ± 3 mOsmol/Kg, particle size of 100.10 ± 1.50 nm, and encapsulation efficiency of 98.41% ± 0.23%. Stability tests showed no major quality changes for liposome suspensions stored at 2–8 °C for 2 months. In vitro release studies showed that MTX-TSL exhibited good thermosensitive properties. Experiments performed on BDF1 mice indicated that initiating hyperthermia before drug administration was beneficial for drug accumulation in tumor tissue and that MTX-TSL outperformed free drugs in suppressing tumor growth when combined with appropriate hyperthermia. MTX-TSL can effectively inhibit tumor growth while increasing the drug’s therapeutic index.

This study presents an approach to the multi-objective optimization of hyperthermia-mediated drug delivery using thermo-sensitive liposomes (TSLs) for the treatment of hepatocellular carcinoma. The research focuses on addressing the non-optimal coupling methods that combine thermal treatments and chemotherapy by employing a Multi-Objective Genetic Algorithm (MOGA) optimization process, in order to identify the right combination of design variables to achieve better treatment outcomes. The proposed model integrates Computational Fluid Dynamics (CFD) analysis using the Pennes' Bioheat equation for tissue heating and a convection-diffusion model for drug delivery. The goal is to maximize the fraction of killed cancer cells through the pharmaceutical treatment while minimizing thermal damage to the tissue, aiming to not hinder the drug feeding from the vascular system. The optimization considers several design variables, including heating power, timing, and the number of antenna slots for the microwave heating. Simulations results suggest that a two-slots antenna configuration with a specific heating schedule yields optimal therapeutic outcomes by maximizing drug concentration in the tumor while limiting damage to healthy tissue. The results of the CFD analysis also show a significant improvement in the treatment outcomes compared to non-optimized results proposed previously in the literature, leading to an increase from the 10% up to the 33% for the fraction of killed cells function. The proposed optimization through Genetic Algorithm framework could significantly improve patient-specific treatment planning for hyperthermia-mediated drug delivery.

Macrophage activation induces rapid proliferation and division of fibroblast-like synovial cells (FLSs), resulting in the degradation of cartilage matrix and bone destruction, which are the main pathological characteristics of rheumatoid arthritis (RA). Inducing apoptosis in these inflammatory cells to mitigate the inflammatory response and alleviate bone damage is a potential therapeutic strategy for RA. In this study, we developed a smart platform for synergistic photothermal therapy (PTT) and chemotherapy by utilizing hyaluronic acid (HA)-modified thermally sensitive liposomes loaded with celastrol (CEL) and gold nanorods (GNRs), termed HA/Lipo-CEL-GNRs, for application in a rat RA model. Under laser irradiation, GNRs exhibited excellent photothermal effects due to localized surface plasmon resonance. The resulting increase in temperature not only effectively eliminated hyperproliferative inflammatory cells in the joints but also triggered CEL release from the thermosensitive liposomes, significantly increasing its concentration in the synovium. The synergistic effect of PTT and chemotherapy significantly promoted the apoptosis of FLSs and macrophages and effectively suppressed the inflammatory response in the RA microenvironment. In summary, multifunctional thermosensitive HA/Lipo-CEL-GNRs represent promising nanotherapeutic platforms capable of achieving light-driven enrichment of heat and therapeutic agents, significantly preventing the progression of RA.

Abstract The precise detection of multiple microRNAs (miRNAs) is of great significance to the classification of various cell subtypes. However, miRNA detection is hindered by signal leakage, false‐positive signals and low expression of miRNAs. Herein, a DNA nanodevice in the second near infrared region (NIR‐II, 1000‐1700 nm) (DND‐II) is developed for dual miRNAs bioimaging based on “AND” logic‐gate signal amplification strategy. The spatiotemporally controlled logic‐gate‐based DND‐II is fabricated by thermosensitive liposomes integrated with the second near‐infrared DNA probes. In particular, the “always‐on” photoacoustic signal of DNA probes provided an additional imaging tool to monitor the distribution of DND‐II in vivo. When both miRNAs are present, the DNA probes generated a “turn on” fluorescent signal through DNA logical analysis and molecular computation, further triggering an entropy‐driven dual‐cycle fluorescence signal amplification. The spatiotemporal DND‐II provides a powerful platform for early diagnosis and photothermal ablation of different subtypes of tumor cells.

Breast cancer is one of the significant threats to women's health worldwide, and traditional treatment methods have many limitations. Liposomes, as a novel type of nanocarrier for drugs, have attracted widespread attention due to their unique structural and functional advantages. This paper provides a detailed introduction to the structural composition and preparation methods of liposomes, as well as their diverse applications in breast cancer treatment, including conventional liposomes, long-circulating liposomes, thermosensitive liposomes, pH-sensitive liposomes, and ligand-modified liposomes. It also discusses the progress of liposomes in clinical research. This paper argues that, despite the great potential of liposomes in breast cancer treatment, many challenges remain. Future research should focus on developing stimuli-responsive liposomes, optimizing preparation processes, and enhancing their safety and efficacy in clinical applications to promote liposomes as an important means for the precise treatment of breast cancer.

Oxygen-supplying nanotherapeutics for bacterial septic arthritis via hypoxia-relief-enhanced antimicrobial and anti-inflammatory phototherapy.