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Delivery of a Cancer-Testis Antigen-Derived Peptide Using Conformationally Restricted Dipeptide-Based Self-Assembled Nanotubes.
Verma, Priyanka; Biswas, Saikat; Yadav, Nitin; Khatri, Anjali; Siddiqui, Hamda; Panda, Jiban Jyoti; Rawat, Bhupendra Singh; Tailor, Prafullakumar; Chauhan, Virander Singh.
Afiliação
  • Verma P; International Centre for Genetic Engineering and Biotechnology, New Delhi 110067, India.
  • Biswas S; International Centre for Genetic Engineering and Biotechnology, New Delhi 110067, India.
  • Yadav N; International Centre for Genetic Engineering and Biotechnology, New Delhi 110067, India.
  • Khatri A; International Centre for Genetic Engineering and Biotechnology, New Delhi 110067, India.
  • Siddiqui H; International Centre for Genetic Engineering and Biotechnology, New Delhi 110067, India.
  • Panda JJ; Institute of Liver and Biliary Sciences, New Delhi 110070, India.
  • Rawat BS; International Centre for Genetic Engineering and Biotechnology, New Delhi 110067, India.
  • Tailor P; Institute of Nano Science and Technology, Mohali, Punjab 140306, India.
  • Chauhan VS; National Institute of Immunology, New Delhi 110067, India.
Mol Pharm ; 18(10): 3832-3842, 2021 10 04.
Article em En | MEDLINE | ID: mdl-34499836
Use of tumor-associated antigens for cancer immunotherapy is limited due to their poor in vivo stability and low cellular uptake. Delivery of antigenic peptides using synthetic polymer-based nanostructures has been actively pursued but with limited success. Peptide-based nanostructures hold much promise as delivery vehicles due to their easy design and synthesis and inherent biocompatibility. Here, we report self-assembly of a dipeptide containing a non-natural amino acid, α,ß-dehydrophenylalanine (ΔF), into nanotubes, which efficiently entrapped a MAGE-3-derived peptide (M3). M3 entrapped in F-ΔF nanotubes was more stable to a nonspecific protease treatment and both F-ΔF and F-ΔF-M3 showed no cellular toxicity for four cancerous and noncancerous cell lines used. F-ΔF-M3 showed significantly higher cellular uptake in RAW 267.4 macrophage cells compared to M3 alone and also induced in vitro maturation of dendritic cells (DCs). Immunization of mice with F-ΔF-M3 selected a higher number of IFN-γ secreting CD8+ T cells and CD4+ T compared to M3 alone. On day 21, a tumor growth inhibition ratio (TGI, %) of 41% was observed in a murine melanoma model. These results indicate that F-ΔF nanotubes are highly biocompatible, efficiently delivered M3 to generate cytotoxic T lymphocytes responses, and able to protect M3 from degradation under in vivo conditions. The F-ΔF dipeptide-based nanotubes may be considered as a good platform for further development as delivery agents.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Testículo / Sistemas de Liberação de Fármacos por Nanopartículas / Antígenos de Neoplasias Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Testículo / Sistemas de Liberação de Fármacos por Nanopartículas / Antígenos de Neoplasias Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2021 Tipo de documento: Article