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Single Protein Encapsulated Doxorubicin as an Efficacious Anticancer Therapeutic

Yu, Changjun and Huang, Faqing and Chow, Warren A. and Cook-Wiens, Galen and Cui, Xiaojiang (2020) Single Protein Encapsulated Doxorubicin as an Efficacious Anticancer Therapeutic. Advanced Therapeutics, 3 (11). Art. No. 2000135. ISSN 2366-3987. https://resolver.caltech.edu/CaltechAUTHORS:20201012-163632149

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Abstract

Small‐molecule chemotherapeutics are potent and effective against a variety of malignancies, but common and severe side effects restrict their clinical applications. Nanomedicine approaches represent a major focus for improving chemotherapy, but have met limited success. To overcome the limitations of chemotherapy drugs, a novel single protein encapsulation (SPE)‐based drug formulation and delivery platform is developed and its utility in improving doxorubicin (DOX) treatment is tested. Using this methodology, a series of SPEDOX complexes are generated by encapsulating various numbers of DOX molecules into a single human serum albumin (HSA) molecule. UV/fluorescence spectroscopy, membrane dialysis, and dynamic light scattering techniques show that SPEDOXs are stable and uniform as monomeric HSA and display unique properties distinct from those of DOX and DOX‐HSA mixture. Furthermore, detailed procedures to precisely monitor and control both DOX payload and binding strength to HSA are established. Breast cancer xenograft tumor studies reveal that SPEDOX‐6 treatment displays improved pharmacokinetic profiles, higher antitumor efficacy, and lower DOX accumulation in the heart tissue compared with unformulated DOX. This SPE technology, which does not involve nanoparticle assembly and modifications to either small‐molecule drugs or HSA, may open up a new avenue for developing new drug delivery systems to improve anticancer therapeutics.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1002/adtp.202000135DOIArticle
ORCID:
AuthorORCID
Yu, Changjun0000-0002-5722-6751
Additional Information:© 2020 Wiley‐VCH. Issue Online: 06 November 2020; Version of Record online: 12 October 2020; Manuscript revised: 02 September 2020; Manuscript received: 08 June 2020. All in vivo evaluations of SPEDOX complexes using mice were conducted at Charles River Laboratory in accordance with the approval of the Charles River Laboratory Institutional Animal Care and Use Committee. This work was financially supported by Sunstate Biosciences, LLC. Xiaojiang Cui is supported by National Institutes of Health (2R01CA151610), Department of Defense (W81XWH‐18‐1‐0067). The authors would like to thank Professor Robert H. Grubbs at California Institute of Technology for providing valuable discussion and comments regarding a draft manuscript. Conflict of Interest: The author C. J. Yu is a named inventor for patent applications regarding “Single Protein‐Encapsulated Pharmaceutics for Enhancing Therapeutic Effects” in pending. The other authors declare no conflict of interest.
Funders:
Funding AgencyGrant Number
Sunstate Biosciences, LLCUNSPECIFIED
NIH2R01CA151610
Department of DefenseW81XWH-18-1-0067
Subject Keywords:chemotherapy, doxorubicin, human serum albumin, single protein encapsulation, SPEDOX
Issue or Number:11
Record Number:CaltechAUTHORS:20201012-163632149
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20201012-163632149
Official Citation:Yu, C., Huang, F., Chow, W.A., Cook‐Wiens, G. and Cui, X. (2020), Single Protein Encapsulated Doxorubicin as an Efficacious Anticancer Therapeutic. Adv. Therap., 3: 2000135. https://doi.org/10.1002/adtp.202000135
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:106005
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:13 Oct 2020 16:28
Last Modified:10 Nov 2020 21:11

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