Rethinking anticancer nanoparticles from a biosafety perspective

A commentary published in Biofunctional Materials systematically discusses key issues regarding the biosafety of anticancer nanoparticles, involving risks arising from drug payloads, nanomaterial accumulation, and bio-corona formation. The article further provides a series of measures to improve safety, including adopting biodegradable materials, implementing surface engineering, and developing organ-specific delivery systems, aiming to promote the development of nanomedicine in a safer and more efficient direction.

As cancer continues to pose significant challenges to global healthcare systems, the emergence of nanomedicine has brought renewed hope for more effective treatments. The unique characteristics of nanoparticles—including the small size, enhanced permeability, and targeting capabilities—make them promising carriers for anticancer drug delivery. However, the rapid advancement of this technology has outpaced systematic evaluation of its potential biosafety risks, creating an urgent need for comprehensive safety assessment protocols.

A research team from Jinan University has recently addressed this critical gap through a detailed analysis published in BM. The review, led by Dr. Zhengwei Huang and first author Naixuan Deng, systematically examines the multifaceted safety concerns associated with anticancer nanoparticles. "While nanomedicine offers promising therapeutic possibilities, we must ensure that safety considerations keep pace with innovation," emphasizes Dr. Huang. "Our analysis reveals that the toxicity of nanoparticles involves not only the encapsulated drugs but also the carrier materials themselves and their complex interactions with biological systems"

The researchers identify three primary sources of potential toxicity: the payload, the nanomaterial carriers, and the dynamic bio-corona formed when nanoparticles enter biological environments. Even when successfully encapsulated within nanoparticles, chemotherapeutic agents like doxorubicin maintain their inherent toxicity properties, with potential leakage or prolonged circulation leading to unintended accumulation in healthy tissues. Temperature and pH-responsive delivery systems present additional challenges, as physiological variations can trigger premature drug release in non-targeted areas.

Nanomaterial carriers themselves pose significant safety concerns. Lipid-based nanoparticles can trigger complement activation and allergic reactions, while metallic nanoparticles such as gold and silver nanoparticles, exhibit size-dependent toxicity and tend to accumulate in vital organs. The degradation products of these materials, particularly metal ions released during nanoparticle breakdown, can interfere with cellular pathways and induce oxidative stress even at low concentrations.

Perhaps the most complex challenge is the formation of bio-corona—where biomolecules spontaneously adsorb onto the surface of nanoparticles in biological environments. These dynamic layers can fundamentally alter the behavior of nanoparticles, obscuring targeting molecules and promoting immune recognition. "The formation of bio-corona represents a critical factor that can completely change how nanoparticles interact with biological systems," explains Deng. "The composition of these coronas varies between individuals, making standardized safety assessment particularly challenging."

In response to these identified risks, the research team proposes various approaches to enhance the safety of nanoparticle. They advocate for selecting drugs with higher tumor cell selectivity and implementing advanced surface modifications to improve targeting specificity. The use of naturally derived, biodegradable materials such as lecithin and albumin is recommended to reduce the risk of long-term accumulation. To address the challenges posed by bio-corona, the researchers suggest implementing antifouling strategies using biomimetic surface coatings to resist protein adsorption.

The team also emphasizes the importance of developing organ-specific delivery strategies, such as inhalable nanoformulations for lung cancer and topical applications for skin cancer, to reduce off-target exposure. These approaches, combined with comprehensive toxicological evaluation standards, could significantly improve the safety characteristics of anticancer nanoparticles.

Looking forward, researchers stress that thorough safety assessment should become a central part of nanomedicine development. This involves detailed studies on how these drugs behave in the body and their long-term effects. Dr. Huang concluded, "We can’t just focus on whether the treatment works; we must also ensure its safety. Only by addressing safety concerns can nanomedicine truly deliver on its promise."

The research team hopes their comprehensive analysis will inspire more systematic safety evaluations in nanomedicine development, ultimately leading to more reliable and clinically viable cancer treatments.

This paper ”Revisit the biosafety of anticancer nanoparticles” was published in Biofunctional Materials.
Deng N, Huang Y, Gao Y, Wu C, Huang Z. Revisit the biosafety of anticancer nanoparticles. Biofunct. Mater. 2025(4):0016, https://doi.org/10.55092/bm20250016.