New Technique Improves Chemotherapy Nano-drug Delivery, Reduces Toxicity
등록일 2019년 01월 07일 수요일
수정일 2017년 11월 29일 수요일

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A new method has been developed to deliver anticancer nano-drugs that increases bioavailability and reduces toxicity.The researchers from the Carnegie Mellon University developed the new methodology.

In their study, the researchers used a nutrition source called Intralipid, approved by the Food and Drug Administration, before the administration of the chemotherapy.Intralipid is used to provide calories to patients through intravenous administration.The nutrition source includes specific nutrients like essential fatty acids.It may also be used to prevent or treat symptoms of essential fatty acid deficiency such as scaly skin and poor wound healing.

The researchers tested their new method in rat models using three FDA approved chemotherapy nano-drugs – Abraxane, Marqibo, and Onivyde.They also used an experimental platinum-containing chemotherapy nano-drug.Prior to the administration, they administered Intralipid to dampen the reticuloendothelial system which is a network of cells and tissues found in blood, connective tissue, spleen, liver, lungs, lymph nodes, and the bone marrow.This procedure is conducted to reduce the toxic side effects of chemotherapy drugs.Typically, chemotherapy drugs are absorbed by various cells including the ones in the liver, kidneys, and spleen after being introduced to the body.Only 0.7 percent of the medication reaches its target tumor.Since healthy cells absorb the drugs, multiple administration can cause toxicity that potentially affects the patient's quality of life.

The researchers found that administration of Intralipid one hour prior to the chemotherapy reduces the drug levels in liver, kidneys, and spleen.The method also reduced the anticancer drugs' side effects in the rat models.They also discovered that Intralipid use has no harmful effect on the tumor growth.Intralipid also did not affect the efficacy of the anticancer drugs.

"This methodology could have a major impact in the delivery of nanodrugs not only for patients undergoing chemotherapy for cancer treatment but also for those being treated with nano-drugs for other conditions," said Chien Ho, a professor at the Department of Biological Sciences at CMU.

Nanotechnology in Cancer Treatment

Nanotechnology allows targeted cancer treatment compared to surgery, radiation, and chemotherapy, that can damage healthy tissues or fail to completely kill all cancer cells.With nanotechnology, clinicians and scientists can create new therapeutic models to treat the disease.

1.Delivery of chemotherapy to target tumor cellsThe main advantage of nanotechnology in cancer treatment is the creation of very small drug carriers.These nanocarriers have an adjustable size and surfaces to accommodate the therapeutic method.They can reach target tumors with enhanced permeability and retention effect.As a result, the patient receives the chemotherapy with low levels of toxicity.Additionally, nano-carriers may be controlled using triggers, such as pH level, heat or ultrasound.

2.Immune response triggered by nanoparticlesImmunotherapy is an optional cancer treatment wherein the immune system is used to fight the disease.But immunotherapy combined with nanotechnology is a new method currently under research.Scientists are looking into the possible use of nanoparticles to deliver molecules that stimulate or modulate the immune system.Nanoparticle vaccines are also being studied on how these can be used to kill tumors.The idea is to increase the number of T cell to destroy cancer cells through the use of several antigens.

3.Augmentation of radiation therapyBlasting radiation on cancer cells induce apoptosis or cell death.The radiation can directly damage DNA or create charged particles that damage DNA in cancer cells.However, radiation therapy damages all types of cells -- healthy or abnormal.Patients receive reduced levels of radiation to avoid damaging healthy tissues and organs.With nanotechnology, radiation therapy like photodynamic therapy may be delivered directly to tumors.It can attack the tumor deep inside tissues and kill radiotherapy-resistant ones without exposing the patient to dangerous radiation levels.

4.Administration of gene therapyGene therapy involves the use of genetic materials like DNA or RNA to treat diseases.Clinicians insert a specific gene into the patient's cells to treat the disorder.The method may be used to replace missing genes or install viruses to attack pathogens.In cancer treatment, gene therapy may use engineered viruses to destroy cancer cells.Adenovirus, reovirus, measles virus, herpes simplex virus, Newcastle disease virus, and vaccinia virus are currently being tested as oncolytic agents.Nanotechnology can be used to optimize the delivery system and stability of gene therapy.

Approved Oncolytic Agents

The Talimogene laherparepvec is based on the herpes simplex virus and has been successful in its phase III clinical trials in 2013 for melanoma.It has been approved by the US FDA for the treatment of melanoma in patients with inoperable tumors in 2015.It has been tested in phase I clinical trials for pancreatic cancer, and phase III trials for cancers of the head and neck.

Other oncolytic agents include Oncorine based on the adenovirus, approved in China for cancers of the head and neck, and RIGVIR based on the enterovirus, approved in Armenia, Georgia, and Latvia for melanoma.

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