Tumor-targeting albumin nanoparticles as an efficacious drug delivery system and potential diagnostic tool in non-muscle-invasive bladder cancer therapy

Sneha Sree Mullapudi; Juwita Norasmara Rahmat; Ratha Mahendran; Yew Koon Lim; Lee Ting Ong; Kah Ying Wong; Edmund Chiong; En-Tang Kang; Koon Gee Neoh

doi:10.1016/j.nano.2022.102600

Tumor-targeting albumin nanoparticles as an efficacious drug delivery system and potential diagnostic tool in non-muscle-invasive bladder cancer therapy

Nanomedicine. 2022 Nov:46:102600. doi: 10.1016/j.nano.2022.102600. Epub 2022 Sep 5.

Authors

Sneha Sree Mullapudi¹, Juwita Norasmara Rahmat¹, Ratha Mahendran², Yew Koon Lim², Lee Ting Ong², Kah Ying Wong², Edmund Chiong³, En-Tang Kang⁴, Koon Gee Neoh⁵

Affiliations

¹ Department of Biomedical Engineering, National University of Singapore, Kent Ridge 117583, Singapore.
² Department of Surgery, National University of Singapore, Kent Ridge 119228, Singapore.
³ Department of Surgery, National University of Singapore, Kent Ridge 119228, Singapore; Department of Urology, National University Hospital, Kent Ridge 119074, Singapore.
⁴ Department of Chemical and Biomolecular Engineering, National University of Singapore, Kent Ridge 117585, Singapore.
⁵ Department of Chemical and Biomolecular Engineering, National University of Singapore, Kent Ridge 117585, Singapore. Electronic address: chenkg@nus.edu.sg.

PMID: 36064034
DOI: 10.1016/j.nano.2022.102600

Abstract

Current intravesical chemotherapy for non-muscle invasive bladder cancer (NMIBC) has limited efficacy due to loss of the instilled agent from urine voiding and the agent's lack of specificity for the tumors. We developed a nanocarrier (txCD47-HNP, ∼100 nm) based on human serum albumin conjugated with a peptide that targets the cluster of differentiation 47 receptor overexpressed on bladder cancer (BC) cells. The IC₅₀ of gemcitabine elaidate (GEM) loaded in the txCD47-HNP was almost an order of magnitude lower than that of free GEM. In a mouse orthotopic BC model, GEM loaded in txCD47-HNP effectively reduced the tumor burden. Tumor cells in BC patients' urine can also be targeted by fluorescence-labeled txCD47-HNP resulting in >83 % of the cells exhibiting fluorescence. Thus, txCD47-HNP can potentially be a theranostic agent in NMIBC management by serving as a targeted drug delivery vehicle as well as an alternative to urine cytology.

Keywords: Albumin nanoparticles; Bladder cancer; CD47 targeting; Intravesical chemotherapy; Urine cytology.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Albumins
Animals
Deoxycytidine / therapeutic use
Drug Delivery Systems / methods
Humans
Mice
Nanoparticles*
Urinary Bladder Neoplasms* / diagnosis
Urinary Bladder Neoplasms* / drug therapy
Urinary Bladder Neoplasms* / pathology

Substances

Deoxycytidine
Albumins