Long circulating photoactivable nanomicelles with tumor localized activation and ROS triggered self-accelerating drug release for enhanced locoregional chemo-photodynamic therapy
Abstract
Although chemo-photodynamic therapy demonstrates promising synergetic therapeutic effect in malignant cancers, the currently available nanocarriers offer the limited capabilities for selective toxicity, drug release and tumor penetration. Herein, we developed photoactivatable nanomicelles, which are constructed by self-assembling of poly (ethylene glycol) (PEG)-stearamine (C18) conjugate (PTS) with a ROS-sensitive thioketal linker (TL) and co-loaded with doxorubicin (DOX) and photosensitizer pheophorbide A (PhA), for enhanced locoregional chemo-photodynamic therapy. Upon accumulation in tumor region, the resulting PTS nanomicelles loaded with Dox and PhA (PTS-DP) demonstrated reactive oxygen species (ROS) cascade responsive release of the DOX and PhA loaded inside. Initial intracellular release of DOX and PhA from the PTS-DP was triggered by the intrinsic presence of endogenous ROS within cancer cells. Furthermore, upon laser irradiation on the tumor region, enhanced singlet oxygen (1 O 2) was generated by PhA released initially in cancer cells, which in turns accelerated the cytoplasmic release of DOX through rapid dissociation of nanomicelles. The gradual elevation of local ROS level generated by light-activated PhA subsequent ROS-triggered release of DOX synergistically inhibited tumor growth and enhances the anti-tumor immunity. Findings of our study suggested that ROS-sensitive PTS nanomicelles could be a promising and innovative nanocarrier for locoregional chemo-photodynamic therapy.
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To enhance the chemical and PDT treatment, Dox and photosensitive pheophorbide A are successfully encapsulated into the developed nanomicelles.
“To enhance the chemical and PDT treatment, Dox and photosensitive pheophorbide A are successfully encapsulated into the developed nanomicelles.”
From Recent Advances in Nanomicelles Delivery Systems. (2020) · cites this paper as [221]
Laser irradiation of the tumor cells results in fast dissociation of nanomicelles and rapid release of DOX.
“Laser irradiation of the tumor cells results in fast dissociation of nanomicelles and rapid release of DOX (Figure 15).”
From Recent Advances in Nanomicelles Delivery Systems. (2020) · cites this paper as [221]
New nanomicelles were constructed via PEG-stearyl amine self-assembly.
“Similarly, new nanomicelles were constructed via PEG-stearyl amine self-assembly [221].”
From Recent Advances in Nanomicelles Delivery Systems. (2020) · cites this paper as [221]
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Self-citation
- Authors
- Uthaman, S., Pillarisetti, S., Mathew, A. P., Kim, Y., Bae, W. K., Huh, K. M., & Park, I.-K.
- Affiliations
- Chungnam National University (KR)
- Chonnam National University (KR)
- Chonnam National University Hwasun Hospital (KR)
- Corresponding author
- Huh, Kang Moo
- Park, In-Kyu
- ORCID
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2020-02
- Volume
- 232
- Pages
- 119702
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2998097855
- Cited by
- 87
- References
- 34
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 11 · 2023: 16 · 2022: 16 · 2021: 19 · 2020: 10
- FWCI
- 3.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Science ICT and Future Planning
- Ministry of Trade, Industry and Energy (10060059, NRF-2017M3A9E2056374)
- Ministry of Science, ICT and Future Planning
- National Research Foundation of Korea (2018R1A5A2024181)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Keywords
- chemo-photodynamic therapy, reactive oxygen species-responsive release, thioketal linker, doxorubicin, pheophorbide a, photosensitizers, singlet oxygen, anticancer drug delivery, nanocarriers, antitumor immunity
- MeSH terms
- Doxorubicin, Neoplasms, Photochemotherapy, Photosensitizing Agents, Reactive Oxygen Species, Nanoparticles, Drug Liberation
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