Abstract
As a nascent and emerging field that holds great potential for precision oncology, nanotechnology has been envisioned to improve drug delivery and imaging capabilities through precise and efficient tumor targeting, safely sparing healthy normal tissue. In the clinic, nanoparticle formulations such as the first-generation Abraxane® in breast cancer, Doxil® for sarcoma, and Onivyde® for metastatic pancreatic cancer, have shown advancement in drug delivery while improving safety profiles. However, effective accumulation of nanoparticles at the tumor site is sub-optimal due to biological barriers that must be overcome. Nanoparticle delivery and retention can be altered through systematic design considerations in order to enhance passive accumulation or active targeting to the tumor site. In tumor niches where passive targeting is possible, modifications in the size and charge of nanoparticles play a role in their tissue accumulation. For niches in which active targeting is required, precision oncology research has identified targetable biomarkers, with which nanoparticle design can be altered through bioconjugation using antibodies, peptides, or small molecule agonists and antagonists. This review is structured to provide a better understanding of nanoparticle engineering design principles with emphasis on overcoming tumor-specific biological barriers.
Highlights
Humanity’s earliest exploration of nanomaterials dates back to the 14th century B.C., when metallic nanoparticles, composed of gold and silver, were used to improve optical properties and visual aesthetics of glass artifacts [1]
The key advantages of NPs include their unique biological interactions based on their physical and chemical properties including charge, size, shape, and surface chemistry. Their high surface area to volume ratio allows for loading therapeutics at a high concentration and dense display of targeting ligands, which can increase the localized effect by controlled release of the drug within targeted cells [9,10]
We summarize the design criteria that guide the use of nanoparticles in cancer medicine in relation to the respective tumor niches/biological barriers
Summary
Humanity’s earliest exploration of nanomaterials dates back to the 14th century B.C., when metallic nanoparticles, composed of gold and silver, were used to improve optical properties and visual aesthetics of glass artifacts [1]. While PEGylation has been shown to increase circulation time and an escape from being cleared by the MPS and RES, organspecific architecture and resulting vascular permeability present many unique challenges to the distribution and uptake of NPs. One illustrative example is that of the blood-brain barrier (BBB), which highly regulates the exposure of the brain to the systemic environment.
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