Formulation for the Targeted Delivery of a Vaccine Strain of Oncolytic Measles Virus (OMV) in Hyaluronic Acid Coated Thiolated Chitosan as a Green Nanoformulation for the Treatment of Prostate Cancer: A Viro-Immunotherapeutic Approach

Abstract

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 surfacefunctionalized 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-α 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 2.34×107 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.

CD44 targeted delivery of oncolytic Newcastle disease virus encapsulated in thiolated chitosan for sustained release in cervical cancer: a targeted immunotherapy approach

“…Morphological and physiochemical characterization of HA-ThCs-NDV revealed that the nanoparticle size was 290.4nm, zeta potential was 22.3 mV with 0.265 PDI. These results are in accordance with our earlier study that reported NP size of 275.6 mm, ± 11.5mV zeta potential and PDI = 0.372 for targeted delivery of oncolytic measles virus loaded into polymeric thiolated chitosan nanoparticles and targeted against CD44 receptors in prostate cancer cells ( 36 ). Another study reported encapsulation of NDV in chitosan nanoparticles with particle size of 371nm and a zeta potential of +2.84 mV ( 37 ).…”

“…These findings suggest that CD44 receptor mediated uptake of HA-ThCs-NDV produced a greater oncolytic effect in HeLa cells as compared to naked NDV virus. Another study reported similar high cytopathic effect of HA functionalized thiolated chitosan encapsulated oncolytic measles virus against prostate cancer cells with IC 50 of 5.1 and 3.52 for pure measles and NPs loaded NDV ( 36 ).…”

Enhancing therapeutic efficacy: sustained delivery of 5-fluorouracil (5-FU) via thiolated chitosan nanoparticles targeting CD44 in triple-negative breast cancer

“…Regardless of the different routes of administration for therapeutic moieties, the particle size and shape have a protruding influence on the transport rate and diffusion mechanism of nanoparticles inside the cell matrix.

Figure 5 SEM images ( A : upper) show spherical and smooth surfaces of nanoparticles of Empty HA-ThCs and ( B : upper) HA-coated 5-FU in ThCs-NPs at the scale of 5.0um while the TEM images ( A : lower) showed more precise images of spherical and smooth surfaces of Empty HA-ThCs and ( B : lower) HA-coated 5-FU in ThCs-NPs at scale of 50 nm and 200 nm 23 , 24 , 35 .

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“…Measuring drug content in the solution surrounding the nanoparticles indirectly reflects the amount of drug incorporated within the nanoparticles. This method was employed to quantify the amount of 5-FU loaded into the nanoparticles by ionic gelation method and to determine the encapsulation efficiency of these formulations 35 . The nanoparticle formulation was centrifuged at 13,700 rpm for 1 h to perform this analysis.…”

Hyaluronic Acid-Mediated Phenolic Compound Nanodelivery for Cancer Therapy

“…These hydroxyls are also able to chelate metal ions and, thus, hamper the metal-catalyzed generation of reactive oxygen substances (ROS) and their oxidant activity. According to our research of the literature, the flavonoids that have been included in HA-coated delivery nanosystems investigated against cancer in the last 5 years are the two flavonols: kaempferol [34] and quercetin (QU) [35][36][37][38][39][40][41], the flavanol epigallocatechin-3-gallate (EGCG) [42][43][44][45][46][47] the flavanone naringenin [48], the isoflavone formononetin [49], and a mix of anthocyanins extracted from corn [50]. Between brackets are reported the number of compounds belonging to each class or subclass according to this classification.…”