1. Academic Validation
  2. Protein corona-guided delivery of dextran-PLGA NPs for enhanced dendritic cell uptake, maturation and improved cancer immunotherapy

Protein corona-guided delivery of dextran-PLGA NPs for enhanced dendritic cell uptake, maturation and improved cancer immunotherapy

  • J Control Release. 2026 Apr 10:392:114733. doi: 10.1016/j.jconrel.2026.114733.
An Thi Thanh Vu 1 Prabhat Shrestha 2 Thu-Huyen Le Thi 2 Anil Giri 2 Khang-Yen Pham 3 Thoa Thi Kim Nguyen 4 Jinkyung Cho 5 Seho Kweon 6 Na Kyeong Lee 7 In-Sun Hong 8 Taeg Kyu Kwon 9 Jong-Sun Kang 10 Jee-Heon Jeong 4 Simmyung Yook 11
Affiliations

Affiliations

  • 1 College of Pharmacy, Keimyung University, Daegu 42601, Republic of Korea.
  • 2 Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea.
  • 3 Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea; School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
  • 4 Department of Precision Medicine, School of Medicine, Sungkyunkwan University, Suwon 16419, Republic of Korea.
  • 5 College of Sport Science, Sungkyunkwan University, Suwon 16419, Republic of Korea.
  • 6 College of Pharmacy, Chonnam National University, Gwangju 61186, Republic of Korea.
  • 7 College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.
  • 8 Department of Molecular Medicine, School of Medicine, Gachon University, Incheon 406-840, Republic of Korea.
  • 9 Department of Immunology, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea.
  • 10 Department of Molecular Cell Biology, School of Medicine, Sungkyunkwan University, Suwon 16419, Republic of Korea.
  • 11 Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea; School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address: [email protected].
Abstract

The formation of a protein corona (PC) significantly influences the behavior of nanoparticles (NPs) in biological fluids; however, its impact on immune modulation and therapeutic efficacy has not been completely understood. The dextran coating of NPs has demonstrated promising effects, including Complement System activation and enhanced immune cell uptake. The stimulator of interferon genes (STING) pathway plays a vital role in coordinating innate and adaptive immunity, making STING agonists attractive candidates for Cancer Immunotherapy. In this study, we developed dextran-coated PLGA nanoparticles loaded with SR717 (Dex-PLGA@SR717 NPs) for enhanced uptake by immature dendritic cells (iDCs) and for promoting tumor-targeted immune activation. Following incubation with human serum (HS), Dex-PLGA NPs formed a PC enriched in the complement component C3, which resulted in superior cellular internalization compared with uncoated PLGA NPs. The significant role of Dex-PLGA@SR717 NPs in promoting iDC maturation and enhancing antigen presentation was confirmed through in vitro studies. This facilitated robust T cell activation and cytotoxicity against B16F10 melanoma cells. Biodistribution analysis revealed preferential accumulation of Dex-PLGA@SR717 NPs in immune-related organs, such as the spleen and lymph nodes, further supporting their immunostimulatory potential. In a murine tumor model, intravenous administration of Dex-PLGA@SR717 NPs (10 mg/kg SR717) was observed to effectively suppressed tumor growth by eliciting a potent antitumor immune response. These findings highlight the potential of Dex-PLGA@SR717 NPs as a promising immunotherapeutic nanoplatform for enhancing dendritic cell-mediated Cancer treatment.

Keywords

Complement protein; Dendritic cell; Nanoparticles; Protein corona; STING pathway; T cells; cancer immunotherapy.

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