Researchers at MD Anderson Cancer Center analyze advanced nanoparticle platforms—liposomes, polymeric, and inorganic systems—for targeted drug delivery, enhanced tumor permeability, and stimuli-responsive release. Functionalized carriers achieve improved drug solubility, precise tumor accumulation, and combined imaging-therapy (theranostics). The review summarizes clinical progress, ongoing trials, and challenges such as biocompatibility barriers and regulatory gaps, outlining strategies to integrate nanomedicines into routine cancer treatment.
Key points
Liposomes, polymeric nanoparticles, and inorganic carriers engineered for passive EPR and active targeting enhance drug solubility and tumor selectivity.
Stimuli-responsive mechanisms and PEGylation strategies enable controlled release, prolonged circulation, and theranostic imaging–therapy integration.
Clinical applications include FDA-approved Doxil, Abraxane, and Onivyde, with ongoing phase III trials but persistent biocompatibility and regulatory challenges.
Why it matters:
Nanomedicine’s targeted nanocarriers promise to revolutionize oncological treatments by improving therapeutic indices and overcoming drug resistance barriers.
Q&A
What is the EPR effect?
How do stimuli-responsive nanoparticles work?
What challenges hinder nanomedicine translation?
What is theranostics in nanotechnology?
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Academy
Enhanced Permeability and Retention (EPR) Effect
The Enhanced Permeability and Retention (EPR) effect is the fundamental principle that allows nanoparticles and other large therapeutic agents to accumulate preferentially in tumor tissue rather than in healthy organs. Tumors grow rapidly and form blood vessels that are irregular and leaky, with gaps between endothelial cells. These gaps typically range from 100 nm to 800 nm, depending on the tumor type. Nanoparticles sized between 50 and 200 nm can passively seep through these gaps and enter the tumor microenvironment.
Once inside, the poor lymphatic drainage of tumor tissue prevents efficient removal of the nanoparticles, leading to prolonged retention. This passive targeting enhances local drug concentrations at the tumor site, maximizing therapeutic effects while minimizing systemic side effects.
Mechanism of EPR in Cancer Nanomedicine
- Leaky Vasculature: Tumor-induced blood vessels are poorly aligned and hyperpermeable, allowing nanoparticles to extravasate through endothelial gaps.
- Impaired Lymphatic Drainage: Tumors lack functional lymphatic vessels, so once nanoparticles enter, they remain in the tumor tissue for extended periods.
- Nanoparticle Size: Optimal size (50–200 nm) ensures nanoparticles exceed renal clearance size (<5 nm) but are small enough to navigate through blood vessels.
Applications in Drug Delivery
Nanotherapeutics leverage the EPR effect to deliver anticancer drugs such as doxorubicin and paclitaxel directly to tumors. Liposomes, polymeric nanoparticles, and inorganic carriers exploit EPR-based passive targeting, often enhanced by surface modifications like polyethylene glycol (PEGylation) to extend circulation time. Active targeting further refines delivery by adding ligands—such as antibodies or peptides—that bind tumor-specific receptors.
Challenges and Variability
Although the EPR effect is widely exploited, it exhibits significant variability between tumor types and among patients. Factors influencing EPR include tumor size, vascular density, and interstitial fluid pressure. Pancreatic and prostate tumors often display a poor EPR profile due to dense stroma, whereas highly vascularized tumors like renal cell carcinoma show stronger EPR. Understanding and measuring EPR in individual patients is crucial for optimizing nanoparticle design and treatment efficacy.
Strategies to Enhance EPR
- Vascular Modulators: Agents such as nitric oxide donors can temporarily increase vascular permeability before nanoparticle administration.
- Hyperthermia: External heating can dilate blood vessels and improve nanoparticle accumulation.
- Enzyme-Responsive Nanocarriers: Tumor-associated enzymes (e.g., matrix metalloproteinases) cleave protective coatings, boosting penetration into the tumor core.
By understanding EPR and these strategies, scientists design smarter nanocarriers that achieve better targeting and drug release, paving the way for more effective and safer cancer treatments.
