Nanobugs as Drugs: Bacterial Derived Nanomagnets Enhance Tumor Targeting and Oncolytic Activity of HSV-1 Virus

TY - JOUR

T1 - Nanobugs as Drugs

T2 - Bacterial Derived Nanomagnets Enhance Tumor Targeting and Oncolytic Activity of HSV-1 Virus

AU - Howard, Faith H.N.

AU - Al-Janabi, Haider

AU - Patel, Priya

AU - Cox, Katie

AU - Smith, Emily

AU - Vadakekolathu, Jayakumar

AU - Pockley, A. Graham

AU - Conner, Joe

AU - Nohl, James F.

AU - Allwood, Dan A.

AU - Collado-Rojas, Cristal

AU - Kennerley, Aneurin

AU - Staniland, Sarah

AU - Muthana, Munitta

N1 - Funding Information: Financial support provided by Cancer Research UK (CRUK grant reference: C25574/A24321), EPSRC for the Kratos LiPPS XPS instrument grant (EP/K005138/1), and the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska Curie grant agreement No 777682 (CANCER). HSV1716 was kindly provided by Virtuu Biologics Ltd. Special thanks to Dario Carugo, University of Southampton for providing the phantom and Devashish Das for the initial MR imaging. Publisher Copyright: © 2022 The Authors. Small published by Wiley-VCH GmbH

PY - 2022/4/1

Y1 - 2022/4/1

N2 - The survival strategies of infectious organisms have inspired many therapeutics over the years. Indeed the advent of oncolytic viruses (OVs) exploits the uncontrolled replication of cancer cells for production of their progeny resulting in a cancer-targeting treatment that leaves healthy cells unharmed. Their success against inaccessible tumors however, is highly variable due to inadequate tumor targeting following systemic administration. Coassembling herpes simplex virus (HSV1716) with biocompatible magnetic nanoparticles derived from magnetotactic bacteria enables tumor targeting from circulation with magnetic guidance, protects the virus against neutralizing antibodies and thereby enhances viral replication within tumors. This approach additionally enhances the intratumoral recruitment of activated immune cells, promotes antitumor immunity and immune cell death, thereby inducing tumor shrinkage and increasing survival in a syngeneic mouse model of breast cancer by 50%. Exploiting the properties of such a nanocarrier, rather than tropism of the virus, for active tumor targeting offers an exciting, novel approach for enhancing the bioavailability and treatment efficacy of tumor immunotherapies for disseminated neoplasms.

AB - The survival strategies of infectious organisms have inspired many therapeutics over the years. Indeed the advent of oncolytic viruses (OVs) exploits the uncontrolled replication of cancer cells for production of their progeny resulting in a cancer-targeting treatment that leaves healthy cells unharmed. Their success against inaccessible tumors however, is highly variable due to inadequate tumor targeting following systemic administration. Coassembling herpes simplex virus (HSV1716) with biocompatible magnetic nanoparticles derived from magnetotactic bacteria enables tumor targeting from circulation with magnetic guidance, protects the virus against neutralizing antibodies and thereby enhances viral replication within tumors. This approach additionally enhances the intratumoral recruitment of activated immune cells, promotes antitumor immunity and immune cell death, thereby inducing tumor shrinkage and increasing survival in a syngeneic mouse model of breast cancer by 50%. Exploiting the properties of such a nanocarrier, rather than tropism of the virus, for active tumor targeting offers an exciting, novel approach for enhancing the bioavailability and treatment efficacy of tumor immunotherapies for disseminated neoplasms.

UR - http://www.scopus.com/inward/record.url?scp=85123501805&partnerID=8YFLogxK

U2 - 10.1002/smll.202104763

DO - 10.1002/smll.202104763

M3 - Article

AN - SCOPUS:85123501805

SN - 1613-6810

VL - 18

JO - Small

JF - Small

IS - 13

M1 - 2104763

ER -