Preparation of PEGylated cationic nanoliposome-siRNA complexes for cancer therapy

Fateme Haghiralsadat1, Ghasem Amoabediny2,3, Samira Naderinezhad2

  • 1a Department of Life Science Engineering , Faculty of New Sciences and Technologies, University of Tehran , Tehran , Iran.

Insights

Stealth PEGylated liposomes enhance small interfering RNA (siRNA) delivery and stability. These novel liposome formulations show great potential for systemic siRNA delivery and improved in vivo stability.

Area of Science:

  • Biotechnology
  • Nanomedicine
  • Gene Delivery

Background:

  • Viral vectors pose challenges for gene delivery.
  • Liposome instability hinders effective small interfering RNA (siRNA) delivery.
  • Non-viral vectors like cationic liposomes are explored to overcome these limitations.

Purpose of the Study:

  • To develop stealth PEGylated liposome formulations for enhanced siRNA delivery.
  • To investigate the impact of PEGylation on liposome characteristics and siRNA complex stability.
  • To evaluate the efficacy of PEGylated liposomes in gene silencing applications.

Main Methods:

  • Formulation of stealth PEGylated liposomes.
  • Characterization of liposome size, zeta potential, and polydispersity index.
  • Assessment of siRNA loading efficiency and long-term stability of siRNA-liposome complexes.
  • Evaluation of intracellular siRNA delivery and gene silencing in MG-63 osteosarcoma cells.

Main Results:

  • PEGylated liposomes demonstrated efficient siRNA loading and prevented aggregation.
  • siRNA-liposome complexes exhibited excellent long-term stability at 4°C for at least 6 months with minimal siRNA release (1-5%).
  • PEGylation significantly improved liposome parameters and enhanced intracellular siRNA delivery, leading to successful J1P1 gene silencing in MG-63 cells.

Conclusions:

  • Novel PEGylated liposomes offer a promising non-viral vector for systemic siRNA delivery.
  • These formulations enhance the in vivo stability of both free siRNA and siRNA lipoplexes.
  • PEGylated liposomes represent a significant advancement in overcoming challenges in siRNA-based therapeutics.

Related Concept Videos

siRNA - Small Interfering RNAs02:30

siRNA - Small Interfering RNAs

Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
18.7K
Cancer Therapies02:49

Cancer Therapies

Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
10.2K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
9.0K
Small interfering RNAs (siRNA)02:30

Small interfering RNAs (siRNA)

4.7K
Gene Therapy00:59

Gene Therapy

Gene therapy is a technique where a gene is inserted into a person’s cells to prevent or treat a serious disease. The added gene may be a healthy version of the gene that is mutated in the patient, or it could be a different gene that inactivates or compensates for the patient’s disease-causing gene. For example, in patients with severe combined immunodeficiency (SCID) due to a mutation in the gene for the enzyme adenosine deaminase, a functioning version of the gene can be...
27.7K
Cationic Chain-Growth Polymerization: Mechanism00:57

Cationic Chain-Growth Polymerization: Mechanism

The cationic polymerization mechanism consists of three steps: initiation, propagation, and termination. In the initiation step of the polymerization process, the π bond of a monomer gets protonated by the Lewis acid catalyst, which is formed from boron trifluoride and water. The protonation of the π bond generates a carbocation stabilized by the electron‐donating group. In the propagation step, the π bond of the second monomer acts as a nucleophile and attacks the...
2.9K