Conjugated Nanoparticles Improve Chemo Drug Delivery

Improving how chemotherapy is delivered to cancer cells is a major concern for researchers and drug manufacturers. One of the big issues with chemotherapy is that most treatment approaches focus on the tumor itself without paying significant attention to the microenvironment surrounding the tumor. Now, investigators at Purdue University have developed new technology aimed at making it easier to deliver cancer treatment to the right “address” in the body while also easing the painful side effects of chemotherapy on patients.

“The traditional approach is similar to a delivery driver trying to drop off a package to a certain person without knowing their specific address,” explained senior study investigator Yoon Yeo, Ph.D., a professor of industrial and physical pharmacy at Purdue. “Our new approach provides directions to find the specific address to deliver the chemotherapeutic drugs.”

Findings from the new study were published recently in Small through an article entitled “Quinic Acid‐Conjugated Nanoparticles Enhance Drug Delivery to Solid Tumors via Interactions with Endothelial Selectins.”

The Centers for Disease Control and Prevention reports that each year about 650,000 cancer patients receive chemotherapy in an outpatient oncology clinic in the United States. Patients receiving chemotherapy are at risk for various side effects that may lead to hospitalization, disruptions in chemotherapy schedules, and even death.

This new methodology uses nanoparticles (NPs), which are considered promising carriers of drugs needed for chemotherapy to target tumors. The researchers developed a technique to prepare polyol-modified nanoparticles, so they locate cancerous cells and tumors by checking out blood vessels surrounding the tumors.

“In recognition of the peritumoral endothelium as a potential barrier in drug delivery to tumors, poly(lactic‐co‐glycolic acid) (PLGA) NPs are modified with a quinic acid (QA) derivative, a synthetic mimic of selectin ligands. QA‐decorated NPs (QA‐NP) interact with human umbilical vein endothelial cells expressing E‐/P‐selectins and induce a transient increase in endothelial permeability to translocate across the layer,” the authors wrote. “QA‐NP reach selectin‐upregulated tumors, achieving greater tumor accumulation and paclitaxel (PTX) delivery than polyethylene glycol‐decorated NPs (PEG‐NP). PTX‐loaded QA‐NP shows greater anticancer efficacy than Taxol or PTX‐loaded PEG‐NP at the equivalent PTX dose in different animal models and dosing regimens. Repeated dosing of PTX‐loaded QA‐NP for two weeks results in complete tumor remission in 40–60% of MDA‐MB‐231 tumor‐bearing mice, while those receiving control treatments succumb to death.

The nanoparticles interact with the vascular lining to enter tumors and destroy them. The Purdue researchers found that their method helps the nanoparticles to exit from the circulation and enter tumors and better treat cancer. They have tested the method on breast cancer and melanoma models and believe it also will prove effective for many types of cancerous tumors.

“Chemotherapy can be almost unbearable for most patients, and we want to change that,” Dr. Yeo concluded. “Our method better targets tumors so lower dosages are required, and the drugs do less damage to normal tissues.”