Prospective vaccination of COVID-19 using shRNA-plasmid-LDH nanoconjugate.

COVID-19 is the pandemic outbreak that is caused by SARS-CoV-2 virus from December, 2019. Human race do not know the curative measure of this devastating disease. In today's era of nanotechnology, it may use its knowledge to develop molecular vaccine to combat this disease. In this article we are intended to propose a hypothesis on the development of a vaccine that is molecular in nature to work against COVID-19. The nanoconjugate may comprise with the inorganic nanoparticle layered double hydroxide intercalated with shRNA-plasmid that have a sequence targeting towards the viral genome or viral mRNA. This nanoconjugate may be used as a nasal spray to deliver the shRNA-plasmid to the target site. The nanoconjugate will have several advantages such as they are biocompatible, they forms as stable knockdown to the target cells and they are stable in the nasal mucosa.

The recent progresses in shRNA-nanoparticle conjugate as a therapeutic approach.

The recent trend of gene therapy is using short hairpin RNA conjugated with different types of nanoparticles. shRNAs have a significant role in gene silencing and have a promising role in treating several genetic and infectious diseases. There are several drawbacks of delivering bare shRNA in the blood as they are fragile in nature and readily degradable. To overcome this problem shRNAs can be conjugated with nanoparticles for a safe deliver. In this article several nanoparticles are mentioned which play significant role in delivery of this payload. On one hand they protect the shRNA from degradation on the other they help to penetrate this large molecule in to the cell. Some of these nanoconjugates are in clinical trials and have a promising role in treatment of diseases.

Prospective treatment of Parkinson's disease by a siRNA-LDH nanoconjugate.

In the world, among the neurodegenerative diseases, Parkinson's is the second most common disease. Although several medications are available in the market, this disease still remains incurable and only the symptoms are controlled to a certain extent with severe side effects. For these reasons we decided to search for a novel therapeutic measure. The objective of this publication was to find a therapeutic procedure to cure this devastating disease. In this study, a biocompatible, easily permeable, cationic nanoparticle-layered double hydroxide was synthesized. Within the layers of these nanoparticles we intercalated α synuclein siRNA, which helps to silence the α synuclein gene. After the intercalation, which was optimized at a 1 : 40 ratio of siRNA : (LDH), we studied its stability in blood by a RNase protection test and serum protection assay. Both proved that LDH was an excellent nanocarrier that can protect intercalated molecules within its layers. After that, several cellular studies were performed by FACS to evaluate its biocompatibility after intercalation and cellular internalization. Results of the biocompatibility studies found it to be nontoxic and in the cellular internalization study, 51.55% of cells were taken into the nanoconjugate and confocal microscopy supported the data from FACS. Lastly, ELISA was performed to discover protein levels in the control, overexpressed, and treated groups of the SH-SY5Y cell line. These results verified that this nanoconjugate is a protective treatment procedure for Parkinson's disease.

siRNA-nanoparticle conjugate in gene silencing: A future cure to deadly diseases?

Alzheimers, cancer, acquired immune deficiency syndrome (AIDS) are considered to be some of the most deadly diseases of the 21st century on account of their severity and rapid increase in the number of affected population and with scarce cases of recovery, they still remain a troubling paradox. Specifically, with millions of cancer patients worldwide and lack of proper cure for the same, understanding the deadly disease at the molecular level and planning a therapeutic strategy in the same line is the need of the hour. Further, the potential threat of prevalence and escalation of Alzheimer's and HIV (human immunodeficiency virus) infection by more than three times as of recent past, needs a medical breakthrough to arrive at a meaningful solution to tackle the present day scenario. It is evident that these diseases initiate and propagate based on certain genes and their expression which needs to be silenced by the help of small interfering RNA (siRNA) by at least 70%. For short term silencing of the protein coding genes, siRNA is the most appropriate tool. Hence, the present communication explores the possibility for treatment and cure of a plethora of deadly diseases, e.g., cancer, including Alzheimer's and AIDS to some extent, emphatically at the molecular level, using the current trend of RNAi (RNA interference) delivery via a wide variety of nanoparticles.

Side-chain amino-acid-based pH-responsive self-assembled block copolymers for drug delivery and gene transfer.

Developing safe and effective nanocarriers for multitype of delivery system is advantageous for several kinds of successful biomedicinal therapy with the same carrier. In the present study, we have designed amino acid biomolecules derived hybrid block copolymers which can act as a promising vehicle for both drug delivery and gene transfer. Two representative natural chiral amino acid-containing (l-phenylalanine and l-alanine) vinyl monomers were polymerized via reversible addition-fragmentation chain transfer (RAFT) process in the presence of monomethoxy poly(ethylene glycol) based macro-chain transfer agents (mPEGn-CTA) for the synthesis of well-defined side-chain amino-acid-based amphiphilic block copolymers, monomethoxy poly(ethylene glycol)-b-poly(Boc-amino acid methacryloyloxyethyl ester) (mPEGn-b-P(Boc-AA-EMA)). The self-assembled micellar aggregation of these amphiphilic block copolymers were studied by fluorescence spectroscopy, atomic force microscopy (AFM) and scanning electron microscopy (SEM). Potential applications of these hybrid polymers as drug carrier have been demonstrated in vitro by encapsulation of nile red dye or doxorubicin drug into the core of the micellar nanoaggregates. Deprotection of side-chain Boc- groups in the amphiphilic block copolymers subsequently transformed them into double hydrophilic pH-responsive cationic block copolymers having primary amino groups in the side-chain terminal. The DNA binding ability of these cationic block copolymers were further investigated by using agarose gel retardation assay and AFM. The in vitro cytotoxicity assay demonstrated their biocompatible nature and these polymers can serve as "smart" materials for promising bioapplications.

Controlled synthesis of pH responsive cationic polymers containing side-chain peptide moieties via RAFT polymerization and their self-assembly.

A general and facile strategy was developed to prepare biocompatible peptide side-chain polymeric materials via reversible addition-fragmentation chain transfer (RAFT) polymerization. Three new dipeptide based monomers, Boc-Phe-Phe-oxyethyl methacrylate (Boc-FF-EMA), Boc-Ile-Phe-oxyethyl methacrylate (Boc-IF-EMA) and Boc-Val-Phe-oxyethyl methacrylate (Boc-VF-EMA), were synthesized and subsequently polymerized by RAFT process to afford well-defined peptide side-chain polymers, P(Boc-dipep-EMA), with controlled molecular weight, narrow polydispersity and precise chain end functionality. Further, a monomethoxy poly(ethylene glycol) (mPEG) based macro-chain transfer agent was employed for RAFT polymerization of these monomers to prepare well defined amphiphilic block copolymers, mPEG-b-P(Boc-dipep-EMA). Subsequent deprotection of side-chain Boc groups produced pH responsive homo- and block copolymers with primary amine moieties at the side chains. The cationic surface charge of various polymeric architectures was studied using dynamic light scattering (DLS) measurements. Atomic force microscopy (AFM) was employed to investigate the self-assembly of block copolymers. The in vitro biocompatibility to HeLa cells was investigated with these polymers to confirm their minimum cytotoxicity. These polymers have great potential for the pH-sensitive delivery of small interfering RNA (siRNA) owing to their interesting phase transition behaviour and biocompatibility.