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Synthesis of a novel, sequentially active-targeted drug delivery nanoplatform for breast cancer therapy.
Satsangi, Arpan; Roy, Sudipa S; Satsangi, Rajiv K; Tolcher, Anthony W; Vadlamudi, Ratna K; Goins, Beth; Ong, Joo L.
Affiliation
  • Satsangi A; Joint Graduate Program in Biomedical Engineering, The University of Texas at San Antonio and the University of Texas Health Science Center at San Antonio, San Antonio, TX 78249, United States; Department of Biomedical Engineering, University of Texas at San Antonio, San Antonio, TX 78249, United Sta
  • Roy SS; Department of Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, United States.
  • Satsangi RK; RANN Research Corporation, San Antonio, TX 78250, United States.
  • Tolcher AW; START - South Texas Accelerated Research Therapeutics, LLC, San Antonio, TX 78229, United States.
  • Vadlamudi RK; Department of Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, United States.
  • Goins B; Department of Radiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, United States.
  • Ong JL; Department of Biomedical Engineering, University of Texas at San Antonio, San Antonio, TX 78249, United States.
Biomaterials ; 59: 88-101, 2015 Aug.
Article in En | MEDLINE | ID: mdl-25956854
ABSTRACT
Breast cancer is the leading cause of cancer deaths among women. Paclitaxel (PTX), an important breast cancer medicine, exhibits reduced bioavailability and therapeutic index due to high hydrophobicity and indiscriminate cytotoxicity. PTX encapsulation in one-level active targeting overcomes such barriers, but enhances toxicity to normal tissues with cancer-similar expression profiles. This research attempted to overcome this challenge by increasing selectivity of cancer cell targeting while maintaining an ability to overcome traditional pharmacological barriers. Thus, a multi-core, multi-targeting construct for tumor specific delivery of PTX was fabricated with (i) an inner-core prodrug targeting the cancer-overexpressed cathepsin B through a cathepsin B-cleavable tetrapeptide that conjugates PTX to a poly(amidoamine) dendrimer, and (ii) the encapsulation of this prodrug (PGD) in an outer core of a RES-evading, folate receptor (FR)-targeting liposome. Compared to traditional FR-targeting PTX liposomes, this sequentially active-targeted dendrosome demonstrated better prodrug retention, an increased cytotoxicity to cancer cells (latter being true when FR and cathepsin B activities were both at moderate-to-high levels) and higher tumor reduction. This research may eventually evolve a product platform with reduced systemic toxicity inherent with traditional chemotherapy and localized toxicity inherent to single-target nanoplatforms, thereby allowing for better tolerance of higher therapeutic load in advanced disease states.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Breast Neoplasms / Drug Delivery Systems / Paclitaxel / Nanostructures / Antineoplastic Agents, Phytogenic Limits: Animals / Female / Humans Language: En Journal: Biomaterials Year: 2015 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Breast Neoplasms / Drug Delivery Systems / Paclitaxel / Nanostructures / Antineoplastic Agents, Phytogenic Limits: Animals / Female / Humans Language: En Journal: Biomaterials Year: 2015 Document type: Article