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A dual-prodrug nanogel combining Vorinostat and Pyropheophorbide a for a high efficient photochemotherapy.
- Source :
-
International journal of pharmaceutics [Int J Pharm] 2024 Aug 15; Vol. 661, pp. 124422. Date of Electronic Publication: 2024 Jul 06. - Publication Year :
- 2024
-
Abstract
- The challenges posed by intractable relapse and metastasis in cancer treatment have led to the development of various forms of photodynamic therapy (PDT). However, traditional drug delivery systems, such as virus vectors, liposomes, and polymers, often suffer from issues like desynchronized drug release, carrier instability, and drug leakage during circulation. To address these problems, we have developed a dual-prodrug nanogel (PVBN) consisting of Pyro (Pyropheophorbide a) and SAHA (Vorinostat) bound to BSA (Bovine Serum Albumin), which facilitates synchronous and spontaneous drug release in situ within the lysosome. Detailed results indicate that PVBN-treated tumor cells exhibit elevated levels of ROS and Acetyl-H3, leading to necrosis, apoptosis, and cell cycle arrest, with PDT playing a dominant role in the synergistic therapeutic effect. Furthermore, the anti-tumor efficacy of PVBN was validated in melanoma-bearing mice, where it significantly inhibited tumor growth and pulmonary metastasis. Overall, our dual-prodrug nanogel, formed by the binding of SAHA and Pyro to BSA and releasing drugs within the lysosome, represents a novel and promising strategy for enhancing the clinical efficacy of photochemotherapy.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Cell Line, Tumor
Mice
Apoptosis drug effects
Drug Liberation
Antineoplastic Agents administration & dosage
Antineoplastic Agents chemistry
Antineoplastic Agents pharmacology
Humans
Reactive Oxygen Species metabolism
Photosensitizing Agents administration & dosage
Photosensitizing Agents pharmacology
Photosensitizing Agents chemistry
Mice, Inbred C57BL
Lung Neoplasms drug therapy
Lung Neoplasms pathology
Melanoma, Experimental drug therapy
Polyethyleneimine chemistry
Vorinostat administration & dosage
Vorinostat pharmacology
Vorinostat chemistry
Photochemotherapy methods
Chlorophyll analogs & derivatives
Chlorophyll chemistry
Chlorophyll administration & dosage
Chlorophyll pharmacology
Serum Albumin, Bovine chemistry
Serum Albumin, Bovine administration & dosage
Nanogels chemistry
Prodrugs administration & dosage
Prodrugs chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3476
- Volume :
- 661
- Database :
- MEDLINE
- Journal :
- International journal of pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 38977163
- Full Text :
- https://doi.org/10.1016/j.ijpharm.2024.124422