Nano–Bio Interactions in Cancer: From Therapeutics Delivery to Early Detection

Abstract

Conspectus Understanding the interactions between nanomaterials and biological systems plays a pivotal role in enhancing the efficacy of nanomedicine and advancing the disease diagnosis. The nanoparticle–protein corona, an active biomolecular layer, is formed around nanoparticles (NPs) upon mixing with biological fluid. The surface layer which consists of rapidly exchanged biomolecules is called the “soft” corona. The inner layer which is more stable and tightly packed is called the “hard” corona. It has been suggested that the NP–protein corona has a decisive effect on the in vivo fate of nanomedicine upon intravenously administration into the mouse. Furthermore, the features of the NP–protein corona make it a powerful platform to enrich low-abundance proteins from serum/plasma for downstream mass-spectrometry (MS)-based proteomics for biomarker discovery and disease diagnosis. Herein, we summarize our recent work on the development of nanomedicine and disease detection from the level of nano–bio interactions between nanoparticles and biological systems. Nanomedicine has made substantial progress over the past two decades. However, the significant enhancement of overall patient survival by nanomedicine remains a challenge due to the lack of a deep understanding of nano–bio interactions in the clinical setting. The pharmacokinetic effect of the protein corona on PEGylated NPs during blood circulation indicated that the adsorbed apolipoproteins could prolong the circulation time of NPs. This mechanistic understanding of the protein corona (active biomolecule) formed around polymeric NPs offered insights into enhancing the efficacy of nanomedicine from the biological interactions point of view. Moreover, we discuss the basic rationale for developing bioresponsive cancer nanomedicine by exploiting the pathophysiological environment around the tumor, typically the pH, reactive oxygen species (ROS), and redox-responsive supramolecular motifs based on synthetic amphiphilic polymers. The protein corona in vivo determines the biological fate of NPs, whereas it opens a new avenue to enrich low abundant proteins in a biospecimen ex vivo to render them “visible” for downstream analytical workflows, such as MS-based proteomics. Blood serum/plasma, due to easy accessibility and great potential to uncover and monitor physiological and pathological changes in health and disease, has remained a major source of detecting protein biomarker candidates. Inspired by the features of the NP–protein corona, a Proteograph platform, which integrates multi-NP–protein coronas with MS for large-scale efficient and deep proteome profiling has been developed. Finally, we conclude this Account with a better understanding of nano–bio interactions to accelerate the nanomedicine translation and how MS-based proteomics can boost our understanding of the corona composition and facilitate the identification of disease biomarkers.

Hard and Soft Protein Corona of Nanomaterials: Analysis and Relevance

“…PC of NMs has been proposed as a diagnostic tool with great potential for biomarker discovery due to the ability of nano-systems to interact with a great variety of proteins [51,[130][131][132]. PC composition is influenced by the choice of biofluid; therefore, it is expected for dif-ferences to be observed between coronas formed on blood samples from healthy and ill patients.…”

Efficacy, Biocompatibility and Degradability of Carbon Nanoparticles for Photothermal Therapy of Lung Cancer

“…Taken together, these results suggest that CNPs possess several desirable properties, including colloidal stability in relevant media. Note, however, that the formation of a protein corona in vivo may influence the pharmacokinetics of nanoparticles and this, therefore, is a topic that requires further exploration in animal models [38]. Even though the CNPs were not functionalized with any targeting agent, they were efficiently internalized by A549 cells and stored as CNP clusters in endosomes.…”

Precision photothermal therapy and photoacoustic imaging by in situ activatable thermoplasmonics

“…Besides acting as phototherapeutic agents, these photo-agents can also serve as imaging probes for allowing both therapeutics and theranostics. [1][2][3][4] For example, photothermal agents increase the environmental temperature upon laser irradiation, generating thermoelastic expansion and acoustic waves, which can be converted to photoacoustic signals. 5 Such photo-based modality holds great potential for disease treatment or diagnosis due to its noninvasiveness, spatiotemporal selectivity, and negligible drug resistance.…”