Nanocarriers: The Future in Cancer Treatment with Selectivity
By Rachel Glantzberg
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Introduction: In an effort to bring more voices to the newsletter I thought it might be a good idea to try and solicit some guest authors. Today, I introduce the very first guest author Rachel Glantzberg, a high school student who is interested in science communication. Rachel got in touch with me via Twitter, we talked for a bit about what she might write, and I kind of pushed her in the direction of nanocarriers (because they can also be made from polymers). I’m not sure how good of an editor I was here, but I hope you enjoy her writing and the topic.
Please welcome Rachel in her first story for The Polymerist. You can find more of here work here. Please share.
Nanocarriers: The Future in Cancer Treatment with Selectivity
Our primary mechanisms for cancer treatment is poison. Having been in a battle with one of medicine’s greatest nuisances since the history of man, one would expect that our means of combat would be more precise. Any of the 1.8 million people diagnosed with cancer in the last year alone1 know that chemotherapy, radiation therapy, and surgery have quite the double effect. As they destroy cancer cells, they also present a markedly brutal impact in patients’ quality of life. The goal of chemotherapy is to destroy any fast-dividing cells, destroying not only cancer cells but atrophying neoplastic cells thus suppressing bone marrow, signaling hair loss, and prompting adverse gastrointestinal effects.2 The inherent lack of specificity of radiation therapy and chemotherapy kills healthy cells in a debilitating fashion. The emerging research on nanocarrier cancer drug delivery restores the dominance of the patient and oncology team and the effect of chemotherapy through “improved stability and biocompatibility, enhanced permeability and retention effect, and precise targeting.”3
The Nanoparticles
Structurally, the minuscule size of nanoparticles serves as the reason for intracellular uptake frequency and is comparable to biomolecules.4 Micromaterials traditionally used are attacked by the immune response of the body, disabling their access to the cancer cells they are intended to fight against. The small proportions of the particles can evade the reticuloendothelial defense mechanism (RDM)—immune responses housed in the cells and tissues of the liver, spleen, blood, and lymph nodes.5 Nanocarriers under 200 nm encapsulate drugs to circulate them through the body, unhindered and undetected by the RDM, better able to directly access the tumors where the supply of drugs are needed. They can enhance the permeability and retention (EPR) effect to have a greater impact where needed, and minimal destruction in places where cytotoxicity does more harm than good.
NPs consist of organic, inorganic, and hybrid variations,6 each with respective attributes for individualized cancer treatment. Organic nanoparticles are advantageous in that they best mimic the biophysical characteristics of living cells and enhance the drug’s efficacy for in vivo cancer drug delivery. These are most often liposome-based NPs, polymer-based NPs, and dendrimers. Inorganic NPs typically have a higher surface area to volume ratio, better enabling the diffusion of inner medicinal contents into cancerous cells.7 This property may be better suited in the avoidance of drug resistance. These are most often gold NPs, carbon nanotubes, silica NPs, magnetic NPs, and quantum dots. Hybrid NPs, as one might presume, combine the best attributes of inorganic and organic carriers with the greatest opportunity for surface modification. They include lipid-polymer hybrid NPs, organic-inorganic hybrid NPs, and cell membrane coated NPs. Nanoparticle variation allows more patient-centered care. Depending on the type of cancer a patient presents with, healthcare providers can methodically select the drug-carriers best suited for the characteristics of that type of drug. For instance, medical professionals have been increasingly using lipopolymers, a hybrid nanoparticle, for the treatment of prostate cancer because of their ability to target prostate specific membrane antigens (PSMA), and target for drugs to synthesize to these biomarkers.8 The type of NP carrier selected will lead to differentiated mechanisms of attack for specialized approaches to care.
Mechanisms for Cell Targeting
Therapeutic agents are targeted via stimuli-responsive factors for both endogenous and exogenous stimuli.9 The means of targeting include passive targeting and active targeting. Passive targeting allows for the localization of nanoparticles within the microenvironment of the tumor. Active targeting is the process by which nanoparticles with a given microenvironment are uptaken by a tumor. Through active and inactive targeting, nanoparticles have routes to better therapeutic efficiency and the reduction of systemic toxicity.10
Passive targeting is how cancerous tissue and normal tissue are differentiated by nanocarriers and ensure specific delivery to cancerous targets.11 Passive targeting can circulate through the bloodstream and attack cancerous cells wherever they may be, typically acting on some component of the cell membrane (receptions, lipid components, antigens, proteins). 12 Cancer cells proliferate rapidly, inducing angiogenesis, the formation of new blood vessels.13 Tumor vessels become hazardously permeable in comparison to healthy vessels. NPs can leak from the blood vessels that supply the tumor and infiltrate the tissue of a tumor. As NPs flood the cell, innate poor lymphatic drainage of cancer provides the mechanics for NPs to remain in the cell.14 The NPs are readily able to release their pharmacological contents into the cell. Passive targeting, however, does present a few restrictions. These include non-specific drug distribution, the variability of the EPR effect existence, and varied blood vessel permeability dependent on the tumor type.15 Nonetheless, the size of nanoparticles is advantageous when used in passive targeting for optimal drug transport via inorganic molecules.
Whereas passive targeting is a free-flowing mechanism in the bloodstream, active targeting is a mechanism where carriers are conjugated to ligands (such as antibodies or peptides) directly at the sight of a tumor.16 Specific targeting ligands are coated on the surface of nanoparticles. An area of much potential in the field of active delivery is liposomes. These are molecules that can be engineered by scientists to mimic the physicochemical properties of lipids.17 This can expedite the lipid exchange that occurs on the surface of cells. This attribute is key in addressing the primary drawback of active targeting: the crucial time-dependence. Many drugs are readily available on the surface of a nanocarrier, which quickly dissociates from that surface in comparison to the passive targeting where drugs are encapsulated beneath the surface level. When these drugs are provided to healthy cells, they negate the potential benefits of nanocarriers; precise delivery with minimal adverse effects in noncancerous cells. When properly delivered, active transport systems are best suited for drug delivery for organic molecules such as nucleic acids.
Nanocarrier development is consistent with an ongoing shift in pharmaceuticals, the inclusion of engineering in the field. While some nanoformulations that have been approved by the FDA, like Abraxane for metastatic breast cancer, nanocarrier’s biocompatibility with the human body stands shrouded in ambiguity.18 Thus, few have been approved for use. Once nanocarrier drug delivery systems have reached a state that their long- and short-term effects are better understood, the benefits for patients and physicians will be huge. Higher intracellular uptake of the drugs through passive and active processes involved with hybrid, organic, and inorganic nanoparticles is an exciting prospect for those struggling with the wrath of cancer. Researchers' commitment to using this technology to its fullest potential is evidenced by the nearly 1,800 patients in over 100 clinical trials in the nanomedicine field.19 Breakthroughs like this reaffirm that to enact big changes, one must start small.
Rachel
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https://www.sciencedaily.com/releases/2017/11/171128160310.htm
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6427334/
https://www.nature.com/articles/s41392-017-0004-3#Sec8
https://www.frontiersin.org/articles/10.3389/fmolb.2020.00193/full