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Blood Interactions, Pharmacokinetics and Depth-Dependent Ablation of Rat Mammary Tumors with Photoactivatable, Liposomal Doxorubicin
摘要： Photosensitizers can be integrated with drug delivery vehicles to develop chemophototherapy agents with anti-tumor synergy between chemo- and photo- components. Long-circulating doxorubicin (Dox) in porphyrin-phospholipid (PoP) liposomes (LC-Dox-PoP) incorporates a phospholipid-like photosensitizer (2 mole %) in the bilayer of Dox-loaded stealth liposomes. Hematological effects of endotoxin-minimized LC-Dox-PoP were characterized via standardized assays. In vitro interaction with erythrocytes, platelets, and plasma coagulation cascade were generally unremarkable while complement activation was found to be similar to that of commercial Doxil. Blood partitioning suggested both the Dox and PoP components of LC-Dox-PoP were stably entrapped or incorporated in liposomes. This was further confirmed with pharmacokinetic studies in Fischer rats, which showed the PoP and Dox components of the liposomes both had nearly identical, long circulation half-lives (25-26 hours). In a large orthotopic mammary tumor model in Fischer rats, following intravenous dosing (2 mg/kg Dox), the depth of enhanced Dox delivery in response to 665 nm laser irradiation was over 1 cm. LC-Dox-PoP with laser treatment cured or potently suppressed tumor growth, with greater efficacy observed in tumors 0.8-1.2 cm compared to larger ones. The skin at the treatment site healed within approximately 30 days. Taken together, these data provide insight into nanocharacterization and photo-ablation parameters for a chemophototherapy agent.
关键词： doxorubicin,chemophototherapy,ablation,nanocharacterization,Liposomes
更新于2025-09-23 15:23:52
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The synthesis and application of nano doxorubicin-indocyanine green matrix metalloproteinase-responsive hydrogel in chemophototherapy for head and neck squamous cell carcinoma
摘要： Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies, with high rates of mortality and morbidity worldwide. Owing to the special anatomical location of this tumor, an effective, minimally invasive treatment with low systemic toxicity is highly desirable. Hydrogels have shown great potential for tumor-targeting therapy, with excellent performance. However, there have been few reports on co-loading photosensitizers and chemotherapeutic drugs into hydrogels. In this study, we synthesized a nano doxorubicin-indocyanine green matrix metalloproteinase (MMP)-responsive hydrogel (denoted as NDIMH), combining chemotherapy and phototherapy, to achieve superior antitumor efficacy. Methods: First, NDIMH was synthesized and characterized by scanning electron microscopy and drug-release assays. Second, the photosensitivity properties and antitumor efficiency of this drug delivery system were studied in vivo and in vitro. Last, the imaging and biodistribution of NDIMH were monitored using the Maestro EX in vivo imaging system. Results: The nanodrugs loaded into the smart hydrogel exhibited uniform size distribution, excellent size stability, and a sustained release in the presence of MMP-2. NDIMH showed ideal photosensitivity characteristics under light. NDIMH with 808 nm near-infrared (NIR) irradiation effectively inhibited the viability, invasion, and metastasis of SCC-15 in vitro. After intratumoral injection of NDIMH with 808 nm NIR illumination, the hydrogels exhibited favorable synergistic antitumor efficacy and acceptable biosafety. Additionally, fluorescence imaging showed that NDIMH could significantly improve the retention of nanodrugs at the tumor site. Conclusion: The intratumoral injection of NDIMH with 808 nm NIR irradiation could be a promising chemophototherapy alternative for HNSCC.
关键词： doxorubicin,MMP-responsive,chemophototherapy,hydrogel,indocyanine green
更新于2025-09-23 15:22:29