Journal
INTERNATIONAL JOURNAL OF NANOMEDICINE
Volume 18, Issue -, Pages 185-205Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S386560
Keywords
green synthesis; controlled release; immunotherapeutic agent; in vitro studies; oncolytic activity; oncolytic measles virus; prostate cancer; targeted virus; drug delivery system; thiolated chitosan; tumour targeting; vaccine-based nanoformulation
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In this study, a polymeric surface-functionalized ligand-based nanoformulation (NF) was developed using a live attenuated oral measles vaccine (OMV) strain. The NFs successfully encapsulated MV and showed sustained release of the virus, leading to significant growth inhibition of prostate cancer cells. This OMV-based nanoformulation provides an active targeted delivery system for oncolytic MV and has the potential for effective cancer treatment at lower doses.
Background: Oncolytic viruses are reported as dynamite against cancer treatment nowadays.Methodology: In the present work, a live attenuated oral measles vaccine (OMV) strain was used to formulate a polymeric surface-functionalized ligand-based nanoformulation (NF). OMV (half dose: not less than 500 TCID units; 0.25 mL) was encapsulated in thiolated chitosan and outermost coating with hyaluronic acid by ionic gelation method characterizing parameters was performed.Results and Discussion: CD44 high expression was confirmed in prostatic adenocarcinoma (PRAD) by GEPIA which extracted data of normal and cancer tissue from GTEx and TCGA. Bioinformatics tools confirmed the viral hemagglutinin capsid protein interaction with human Caspase-I, NLRP3, and TNF-alpha and viral fusion protein interaction with COX-II and Caspase-I after successful delivery of MV encapsulated in NFs due to high affinity of hyaluronic acid with CD44 on the surface of prostate cancer cells. Particle size = 275.6 mm, PDI = 0.372, and +/- 11.5 zeta potential were shown by zeta analysis, while the thiolated group in NFs was confirmed by FTIR and Raman analysis. SEM and XRD showed a spherical smooth surface and crystalline nature, respectively, while TEM confirmed virus encapsulation within nanoparticles, which makes it very useful in targeted virus delivery systems. The virus was released from NFs in a sustained but continuous release pattern till 48 h. The encapsulated virus titer was calculated as 2.34x107 TCID50/mL units, which showed syncytia formation on post-day infection 7. Multiplicities of infection 0.1, 0.5, 1, 3, 5, 10, 15, and 20 of HA-coated OMV-loaded NFs as compared to MV vaccine on PC3 was inoculated with IC50 of 5.1 and 3.52, respectively, and growth inhibition was seen after 72 h via MTT assay which showed apoptotic cancer cell death.Conclusion: Active targeted, efficacious, and sustained delivery of formulated oncolytic MV is a potent moiety in cancer treatment at lower doses with safe potential for normal prostate cells.
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