The therapeutic efficacy and adverse impacts of nanoparticles (NPs) are strongly dependent on their systemic circulation time. The corona proteins adsorbed on the NPs determine their plasma half-lives, and hence, it is crucial to identify the proteins shortening or extending their circulation time. In this work, the in vivo circulation time and corona composition of superparamagnetic iron oxide nanoparticles (SPIONs) with different surface charges/chemistries were analyzed over time. SPIONs with neutral and positive charges showed the longest and shortest circulation times, respectively. The most striking observation was that corona-coated NPs with similar opsonin/dysopsonin content showed different circulation times, implying these biomolecules are not the only contributing factors. Long-circulating NPs adsorb higher concentrations of osteopontin, lipoprotein lipase, coagulation factor VII, matrix Gla protein, secreted phosphoprotein 24, alpha-2-HS-glycoprotein, and apolipoprotein C-I, while short-circulating NPs adsorb higher amounts of hemoglobin. Therefore, these proteins may be considered to be determining factors governing the NP systemic circulation time.

The protein corona effect has long been treated as the evil source behind delivery efficacy issues. In this study, this concept is challenged by showcasing that the protein corona can serve as a versatile functionalization approach to improve the delivery efficacy or mitigate nanocytotoxicity. To this end, the depleted serum is introduced to create nanomaterials carrying functionally distinct protein corona, referred to as PCylated nanomaterials. It is confirmed that the passivation with depleted serum helps reduce the toxicity and pro-inflammatory response. Furthermore, the same method can be leveraged to enhance the capacity of nanomaterials to undergo endocytosis as well as their potential as an agonist for the NF-κB pathways. The comparable stability of protein corona created by late and early-stage serum reveals that the chanceless interaction with nanomaterials, rather than an inadequate binding strength, may be behind the failure of enriching certain components. The PCylation strategy is extended to cancer patient-derived fluid, creating a set of T1 and T3-stage cancer-specific nanotherapeutics to retard the metastasis of cancer cells, while leaving normal endothelial negligibly affected. It is hoped the novel PCylation approach validated here can shed light on the future development of precision nanomedicine with improved delivery efficacy.

Understanding the effects mediated by a set of nanoparticle (NP)-bound host biomolecules, often indicated with the umbrella term of NP corona, is essential in nanomedicine, nanopharmacology, and nanotoxicology. Among the NP-adsorbed proteome, some factors mediate cell binding, endocytosis, and clearing by macrophages and other phagocytes (opsonins), while some others display few affinities for the cell surface (dysopsonins). The functional mapping of opsonins and dysopsonins is instrumental to design long-circulating and nanotoxicologically safe next-generation nanotheranostics. In this review, we critically analyze functional data identifying specific proteins with opsonin or dysopsonin properties. Special attention is dedicated to the following: (1) the simplicity or complexity of the NP proteome and its modulation, (2) the role of specific host proteins in mediating the stealth properties of uncoated or polymer-coated NPs, and (3) the ability of the innate immune system, and, in particular, of the complement proteins, to mediate NP clearance by phagocytes. Emerging species-specific peculiarities, differentiating humans from preclinical animal models (the murine especially), are highlighted throughout this overview. The operative definition of opsonin and dysopsonin and the measurement schemes to assess their in vitro efficacy is critically re-examined. This provides a shared and unbiased approach useful for NP opsonin and dysopsonin systematic identification.

BACKGROUND: The efficacy of chemotherapy is undermined by adverse side effects and chemoresistance of target tissues. Developing a drug delivery system can reduce off-target side effects and increase the efficacy of drugs by increasing their accumulation in target tissues. Inorganic salts have several advantages over other drug delivery vectors in that they are non-carcinogenic and less immunogenic than viral vectors and have a higher loading capacity and better controlled release than lipid and polymer vectors.
METHODS: MgF₂ crystals were fabricated by mixing 20 mM MgCl₂ and 10 mM NaF and incubating for 30 min at 37 °C. The crystals were characterized by absorbance, dynamic light scattering, microscopic observance, pH sensitivity test, SEM, EDX and FTIR. The binding efficacy to doxorubicin was assessed by measuring fluorescence intensity. pH-dependent doxorubicin release profile was used to assess the controlled release capability of the particle-drug complex. Cellular uptake was assessed by fluorescence microscopy. Cytotoxicity of the particles and the drug-particle complex were assessed using MTT assay to measure cell viability of MCF-7 cells.
CONCLUSIONS: Particle size on average was estimated to be <200 nm. The crystals were cubic in shape. The particles were pH-sensitive and capable of releasing doxorubicin in increasing acidic conditions. MgF₂ nanocrystals were safe in lower concentrations, and when bound to doxorubicin, enhanced its uptake. The protein corona formed around MgF₂ nanoparticles lacks typical opsonins but contains some dysopsonins.
CONCLUSIONS: A drug delivery vector in the form of MgF₂ nanocrystals has been developed to transport doxorubicin into breast cancer cells. It is pH-sensitive (allowing for controlled release), size-modifiable, simple and cheap to produce.