In-situ vaccination using dual responsive organelle targeted nanoreactors

Vishnu  Sunil; Anbu  Mozhi; Wenbo Zhan; Jia Heng  Teoh; Pramila Baban  Ghode; Nitish V Thakor; Chi-Hwa Wang

doi:10.1016/j.biomaterials.2022.121843

In-situ vaccination using dual responsive organelle targeted nanoreactors

Vishnu Sunil, Anbu Mozhi, Wenbo Zhan, Jia Heng Teoh, Pramila Baban Ghode, Nitish V Thakor, Chi-Hwa Wang^*

^*Corresponding author for this work

Engineering

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

Abstract

The poor translation of nanomedicines from bench to bedside can be attributed to (i) lack of a delivery system with precise drug compositions with no batch-to-batch variations, (ii) off-target or undesirable release of payload, and (iii) lack of a method to monitor the fate of the specific drug of interest, which often has to be modified with a fluorescent tag or replaced with a model drug which can be tracked. To overcome these translation hurdles, we developed dual responsive organelle targeted nanoreactors (DRONEs) with precise drug composition, site specific payload release and which enable accurate in-vivo monitoring. DRONEs consist of a polyprodrug inner core composed of a dual responsive backbone containing a photosensitizer (Protoporphyrin IX) grafted with functionalized polyethylene glycol (PEG) outer shell to prolong blood circulation and a tumour homing pro-apoptotic peptide (CGKRKD[KLAKLAK]2) (THP). DRONEs can significantly reduce the tumour burden in an orthotopic glioblastoma model due to its BBB penetrating and tumour homing capabilities. DRONEs exhibit good safety profile and biocompatibility along with a reliable route of elimination. DRONEs showed great potential as an in-situ vaccine which can not only eliminate the tumour but also trigger an adaptive immune response which would provide long-term anti-tumoural immunity.

Original language	English
Article number	121843
Number of pages	16
Journal	Biomaterials
Volume	290
Early online date	10 Oct 2022
DOIs	https://doi.org/10.1016/j.biomaterials.2022.121843
Publication status	Published - 1 Nov 2022

Bibliographical note

This project is supported by the Economic Development Board Singapore and National University of Singapore under the grant N279-000-030-001. The project received partial support in the following grants: NAMIC Singapore and funded by the National Research Foundation Singapore under its Innovation Cluster Programme under the project number, 2018239 and grant number, R-279-000- 577-592. Singapore National Research Foundation, Grant No.: R-719-000-018-281. The authors would like to thank Mr. Lim You Kang for all his technical assistance in this project. Vishnu Sunil and Jia Heng Teoh greatly appreciate the National University of Singapore Research Scholarship for the funding of their Ph.D. studies at the National University of Singapore.

Data Availability Statement

The raw/processed data required to reproduce these findings cannot be shared at this time as the data also forms part of an ongoing study

Keywords

in-situ vaccine
dual responsive
backbone shattering
combination therapy
orthotropic glioblastoma
mice model
personalised medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Sunil_etal_Insitu_vaccination_using_AAM
Accepted author manuscript, 2.77 MB
Licence: CC BY-NC-ND
Embargo ends: 10/10/24

Cite this

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abstract = "The poor translation of nanomedicines from bench to bedside can be attributed to (i) lack of a delivery system with precise drug compositions with no batch-to-batch variations, (ii) off-target or undesirable release of payload, and (iii) lack of a method to monitor the fate of the specific drug of interest, which often has to be modified with a fluorescent tag or replaced with a model drug which can be tracked. To overcome these translation hurdles, we developed dual responsive organelle targeted nanoreactors (DRONEs) with precise drug composition, site specific payload release and which enable accurate in-vivo monitoring. DRONEs consist of a polyprodrug inner core composed of a dual responsive backbone containing a photosensitizer (Protoporphyrin IX) grafted with functionalized polyethylene glycol (PEG) outer shell to prolong blood circulation and a tumour homing pro-apoptotic peptide (CGKRKD[KLAKLAK]2) (THP). DRONEs can significantly reduce the tumour burden in an orthotopic glioblastoma model due to its BBB penetrating and tumour homing capabilities. DRONEs exhibit good safety profile and biocompatibility along with a reliable route of elimination. DRONEs showed great potential as an in-situ vaccine which can not only eliminate the tumour but also trigger an adaptive immune response which would provide long-term anti-tumoural immunity.",

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author = "Vishnu Sunil and Anbu Mozhi and Wenbo Zhan and Teoh, {Jia Heng} and Ghode, {Pramila Baban} and Thakor, {Nitish V} and Chi-Hwa Wang",

note = "This project is supported by the Economic Development Board Singapore and National University of Singapore under the grant N279-000-030-001. The project received partial support in the following grants: NAMIC Singapore and funded by the National Research Foundation Singapore under its Innovation Cluster Programme under the project number, 2018239 and grant number, R-279-000- 577-592. Singapore National Research Foundation, Grant No.: R-719-000-018-281. The authors would like to thank Mr. Lim You Kang for all his technical assistance in this project. Vishnu Sunil and Jia Heng Teoh greatly appreciate the National University of Singapore Research Scholarship for the funding of their Ph.D. studies at the National University of Singapore.",

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AU - Thakor, Nitish V

AU - Wang, Chi-Hwa

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M1 - 121843

ER -

In-situ vaccination using dual responsive organelle targeted nanoreactors

Abstract

Bibliographical note

Data Availability Statement

Keywords

UN SDGs

Access to Document

Embargoed Document

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Cite this