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Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
A Photosensitizer Discretely Loaded Nanoaggregate with Robust Photodynamic Effect for Local Treatment Triggers
Hao Zhao1, Jiabao Xu, Yuqiao Wang1
1CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China.
Abstract:
Photodynamic therapy (PDT), is a rising star for suppression of in situ and metastatic tumors, yet it is impeded by low ROS production and off-target phototoxicity. Herein, an aggregation degree editing strategy, inspired by gene editing, was accomplished by the coordination of an aggregation degree editor, p(MEO2MA160-co-OEGMA40)-b-pSS30 [POEGS; MEO2MA = 2-(2-methoxyethoxy)ethyl methacrylate, OEGMA = oligo(ethylene glycol) methacrylate; pSS = poly(styrene sulfonate)] and indocyanine green (ICG) to nontoxic Mg2+, forming an ICG discretely loaded nanoaggregate (ICG-DNA). Optimization of the ICG aggregation degree [POEGS/ICG (P/I) = 6.55] was achieved by tuning the P/I ratio, alleviating aggregation-caused-quenching (ACQ) and photobleaching concurrently. The process boosts the PDT efficacy, spurring robust immunogenic cell death (ICD) and systemic antitumor immunity against primary and metastatic immunogenic "cold" 4T1 tumors via intratumoral administration. Moreover, the temperature-sensitive phase-transition property facilitates intratumoral long-term retention of ICG-DNA, reducing undesired phototoxicity to normal tissues; meanwhile, the photothermal-induced tumor oxygenation further leads to an augmented PDT outcome. Thus, this simple strategy improves PDT efficacy, boosting the singlet oxygen quantum yield (ΦΔ)-dependent ICD effect and systemic antitumor responses via local treatment.
Insights
This study introduces a novel aggregation editing strategy for photodynamic therapy (PDT) using indocyanine green (ICG) nanoaggregates. This approach enhances tumor suppression and systemic immunity while minimizing off-target toxicity.
Area of Science:
- Biomedical Engineering
- Materials Science
- Oncology
Background:
- Photodynamic therapy (PDT) shows promise for cancer treatment but is limited by low reactive oxygen species (ROS) production and off-target phototoxicity.
- Indocyanine green (ICG) is a photosensitizer used in PDT, but its efficacy is often reduced by aggregation-caused quenching (ACQ) and photobleaching.
Purpose of the Study:
- To develop an aggregation degree editing strategy to optimize ICG nanoaggregates for enhanced PDT efficacy.
- To improve ROS production, reduce phototoxicity, and boost antitumor immunity against 'cold' tumors.
Main Methods:
- Coordination of an aggregation degree editor, p(MEO2MA160-co-OEGMA40)-b-pSS30 (POEGS), with ICG and Mg2+ to form discretely loaded nanoaggregates (ICG-DNA).
- Optimization of the POEGS/ICG (P/I) ratio to alleviate ACQ and photobleaching.
- Intratumoral administration of ICG-DNA for treating 4T1 tumors, leveraging temperature-sensitive phase transition and photothermal effects.
Main Results:
- Optimized ICG aggregation degree (P/I = 6.55) significantly alleviated ACQ and photobleaching, boosting PDT efficacy.
- Enhanced immunogenic cell death (ICD) and systemic antitumor immunity against primary and metastatic 4T1 tumors.
- Temperature-sensitive retention and photothermal-induced oxygenation improved therapeutic outcomes and reduced off-target phototoxicity.
Conclusions:
- The aggregation degree editing strategy offers a simple yet effective method to enhance PDT performance.
- ICG-DNA nanoaggregates demonstrate significant potential for treating immunogenic 'cold' tumors through improved ICD and systemic immune responses.
- This approach provides a promising platform for developing advanced PDT strategies with reduced side effects.
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