synthesis-characterization-placental-chondroitin-sulfate-plcsa

Synthesis and Characterization of Placental Chondroitin Sulfate A (plCSA)-Targeting Lipid-Polymer Nanoparticles

An effective cancer therapeutic method reduces and eliminates tumors with minimal systemic toxicity. Actively targeting nanoparticles offer a promising ...

Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences (CAS)

Guangdong Medical University

Oxygen nanocarrier (A/D-ONC) with a polymeric core entrapping hemoglobin and a cationic lipid shell absorbing a DOX-intercalating DNA duplex is developed. After endocytosis oxygenated A/D-ONC donates O2 to cancer cells that acts therapeutically by: (1) increasing intracellular ATP content that promotes DOX release, thereby converting ATP to the trigger of detrimental chemotherapy; (2) by synchronously increasing the ROS amount to amplify the lethality to cancer cells.

Oxygen Nanocarrier for Combined Cancer Therapy: Oxygen-Boosted ATP-Responsive Chemotherapy with Amplified ROS Lethality.

Metastatic triple-negative breast cancer (mTNBC) is an aggressive disease among women worldwide, characterized by high mortality and poor prognosis despite systemic therapy with radiation and chemotherapies. Photodynamic therapy (PDT) is an important strategy to eliminate the primary tumor, however its therapeutic efficacy against metastases and recurrence is still limited. Here, we employed a template method to develop the core-shell gold nanocage@manganese dioxide (AuNC@MnO, AM) nanoparticles as tumor microenvironment responsive oxygen producers and near-infrared (NIR)-triggered reactive oxygen species (ROS) generators for oxygen-boosted immunogenic PDT against mTNBC. In this platform, MnO shell degrades in acidic tumor microenvironment pH/HO conditions and generates massive oxygen to boost PDT effect of AM nanoparticles under laser irradiation. Fluorescence (FL)/photoacoustic (PA)/magnetic resonance (MR) multimodal imaging confirms the effective accumulation of AM nanoparticles with sufficient oxygenation in tumor site to ameliorate local hypoxia. Moreover, the oxygen-boosted PDT effect of AM not only destroys primary tumor effectively but also elicits immunogenic cell death (ICD) with damage-associated molecular patterns (DAMPs) release, which subsequently induces DC maturation and effector cells activation, thereby robustly evoking systematic antitumor immune responses against mTNBC. Hence, this oxygen-boosted immunogenic PDT nanosystem offers a promising approach to ablate primary tumor and simultaneously prevent tumor metastases via immunogenic abscopal effects.

Mingbin Zheng

Guangdong Key Laboratory of Nanomedicine,
CAS Key Lab for Health Informatics,
Guangdong Key Laboratory of Nanomedicine, CAS Key Lab for Health Informatics

Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences (CAS)

Synthesis and Characterization of Placental Chondroitin Sulfate A (plCSA)-Targeting Lipid-Polymer Nanoparticles

Mingbin Zheng

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Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences (CAS)

Synthesis and Characterization of Placental Chondroitin Sulfate A (plCSA)-Targeting Lipid-Polymer Nanoparticles

Guangdong Key Laboratory of Nanomedicine,
CAS Key Lab for Health Informatics,
Guangdong Key Laboratory of Nanomedicine, CAS Key Lab for Health Informatics