Glycodendron/pyropheophorbide-a (Ppa)-functionalized hyaluronic acid as a nanosystem for tumor photodynamic therapy

Xiaoqin Zhang; Yahui Wu; Zhiqian Li; Wenjia Wang; Yaping Wu; Dayi Pan; Zhongwei Gu; Ruilong Sheng; Helena Tomás; Hu Zhang; João Rodrigues; Qiyong Gong; Kui Luo

doi:10.1016/j.carbpol.2020.116749

Glycodendron/pyropheophorbide-a (Ppa)-functionalized hyaluronic acid as a nanosystem for tumor photodynamic therapy

Carbohydr Polym. 2020 Nov 1:247:116749. doi: 10.1016/j.carbpol.2020.116749. Epub 2020 Jul 12.

Authors

Xiaoqin Zhang¹, Yahui Wu², Zhiqian Li², Wenjia Wang², Yaping Wu², Dayi Pan², Zhongwei Gu², Ruilong Sheng³, Helena Tomás³, Hu Zhang⁴, João Rodrigues³, Qiyong Gong², Kui Luo⁵

Affiliations

¹ Huaxi MR Research Center (HMRRC), Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, National Clinical Research Center for Geriatrics, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China; College of Preclinical Medicine, Southwest Medical University, Luzhou, 646000, China.
² Huaxi MR Research Center (HMRRC), Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, National Clinical Research Center for Geriatrics, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
³ CQM - Centro de Química da Madeira, Universidade da Madeira, Campus da Penteada, 9000-390, Funchal, Portugal.
⁴ Amgen Bioprocessing Centre, Keck Graduate Institute, CA 91711, USA.
⁵ Huaxi MR Research Center (HMRRC), Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, National Clinical Research Center for Geriatrics, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China. Electronic address: luokui@scu.edu.cn.

PMID: 32829865
DOI: 10.1016/j.carbpol.2020.116749

Abstract

To enhance the drug delivery efficiency of hyaluronic acid (HA), we designed and prepared glycodendron and pyropheophorbide-a (Ppa)-functionalized HA (HA-Ppa-Dendron) as a nanosystem for cancer photodynamic therapy. Linear Ppa-modified HA (HA-Ppa) was also prepared as a control. Cellular uptake of both polymers by MDA-MB-231 cells led to mitochondrial dysfunction and generation of reactive oxygen species under the irradiation of a laser. Compared to the linear polymer, HA-Ppa-Dendron had higher molecular weight, a more compact nanoscale particle size, and a dendritic structure, resulting in a much longer blood circulation time and higher tumor accumulation. HA-Ppa-Dendron outperformed HA-Ppa in inhibiting cell growth, with 60 % of tumors was eradicated under laser irradiation. Tumor growth inhibition (TGI) up to 99.2 % was achieved from HA-Ppa-Dendron, which was much higher than that of HA-Ppa (50.6 %). Therefore, glycodendron-functionalized HAs by integration of HA and dendritic polymers may act as efficient anti-cancer nanomedicine.

Keywords: Dendrimer; Drug delivery; Hyaluronic acid; Nanomedicines; Photodynamic therapy.

MeSH terms

Animals
Anthracenes / chemistry*
Apoptosis
Breast Neoplasms / drug therapy*
Breast Neoplasms / metabolism
Breast Neoplasms / pathology
Cell Proliferation
Chlorophyll / analogs & derivatives*
Chlorophyll / chemistry
Female
Humans
Hyaluronic Acid / chemistry*
Mice
Mice, Inbred BALB C
Nanoparticles / administration & dosage*
Nanoparticles / chemistry
Photochemotherapy*
Photosensitizing Agents / chemistry
Photosensitizing Agents / pharmacology*
Tumor Cells, Cultured
Xenograft Model Antitumor Assays

Substances

Anthracenes
Photosensitizing Agents
dendron
Chlorophyll
pyropheophorbide a
Hyaluronic Acid