Innate tumor-targeted nanozyme overcoming tumor hypoxia for cancer theranostic use.

INTRODUCTION: Hypoxic tumor microenvironment (TME) is the major contributor to cancer metastasis, resistance to chemotherapy, and recurrence of tumors. So far, no approved treatment has been available to overcome tumor hypoxia. OBJECTIVES: The present study aimed to relieve tumor hypoxia via a nanozyme theranostic nanomaterial as well as providing magnetic resonance imaging (MRI)-guided therapy. METHODS: Manganese dioxide (MnO2) was used for its intrinsic enzymatic activity co-loaded with the anti-cancer drug Doxorubicin (Dox) within the recombinant heavy-chain apoferritin cavity to form MnO2-Dox@HFn. Following the synthesis of the nanomaterial, different characterizations were performed as well as its nanozyme-like ability. This nanoplatform recognizes tumor cells through the transferrin receptors 1 (TfR1) which are highly expressed on the surface of most cancer cells. The cellular uptake was confirmed by flow cytometry and fluorescence spectroscopy. In vitro and in vivo studies have been investigated to evaluate the hypoxia regulation, MRI ability and anti-tumor activity of MnO2-Dox@HFn. RESULTS: Being a TME-responsive nanomaterial, MnO2-Dox@HFn exerted both peroxidase and catalase activity that mainly produce massive oxygen and Mn2+ ions. Respectively, these products relieve the unfavorable tumor hypoxia and also exhibit T1-weighted MRI with a high longitudinal relaxivity of 33.40 mM. s-1. The utility of MnO2-Dox@HFn was broadened with their efficient anti-cancer activity proved both in vitro and in vivo. CONCLUSIONS: MnO2-Dox@HFn successfully overcome tumor hypoxia with double potentials enzymatic ability and diagnostic capacity. This investigation could ignite the future application for cancer theranostic nanozyme therapy.

Apoferritin: a potential nanocarrier for cancer imaging and drug delivery.

Introduction: As a protein-based biomaterial for potential cancer targeting delivery, apoferritin has recently attracted interest.Areas covered: In this review, we discuss the development of this cage-like protein as an endogenous nanocarrier that can hold molecules in its cavity. We present the specific characterizations and formulations of apoferritin nanocarriers, and outline the recent progress of the protein as an appropriate tumor-delivery vehicle in different therapeutic strategies to treat solid tumors. Finally, we propose how the application for cancer drug repurposing delivery within apoferritin could expand cancer treatment in the future.Expert opinion: Being a ubiquitous iron storage protein that exists in many living organisms, apoferritin is promising as a cancer tumor-targeting nanocarrier. By exploiting its versatility, apoferritin could be used for cancer repurposed drug delivery and could reduce the high cost of new drug discovery development and shorten the formulation process.

Formulation optimization of solid self-microemulsifying pellets for enhanced oral bioavailability of curcumin.

Solidification of self-microemulsifying drug delivery systems (SMEDDS) is one of the major trends to promote the transformation of self-microemulsion technology into industrialization. Here, a preliminary curcumin SMEDDS formulation was constructed to improve the druggability of curcumin, through the determination of equilibrium solubility determination, self-emulsifying grading assessment, and pseudo-ternary phase diagrams drafting. Furthermore, the optimal curcumin SMEDDS formulation consisted of 10% Ethyl oleate, 57.82% Cremophor RH 40, and 32.18% Transcutol P was obtained by the simplex lattice design. Besides, curcumin solid self-microemulsifying drug delivery system (S-SMEDDS) was developed by the extrusion and spheronization process to achieve the solidification of SMEDDS. The formulation of curcumin S-SMEDDS pellets was screened by the single factor experiment and the process parameters were investigated using the orthogonal optimization method. Subsequently, curcumin S-SMEDDS pellets were evaluated by apparent morphology characterization, redispersibility study, drug release behavior, and pharmacokinetic evaluation. Results from the pharmacokinetic study in rabbits showed that the AUC0-τ of the curcumin S-SMEDDS pellets and curcumin suspension were 5.91 ± 0.28 µg/mL·h and 2.05 ± 0.04 µg/mL·h, while the relative bioavailability was 289.30%. These studies demonstrated that S-SMEDDS pellets can be a promising strategy for curcumin industrialized outputs.

Applications and developments of gene therapy drug delivery systems for genetic diseases.

Genetic diseases seriously threaten human health and have always been one of the refractory conditions facing humanity. Currently, gene therapy drugs such as siRNA, shRNA, antisense oligonucleotide, CRISPR/Cas9 system, plasmid DNA and miRNA have shown great potential in biomedical applications. To avoid the degradation of gene therapy drugs in the body and effectively deliver them to target tissues, cells and organelles, the development of excellent drug delivery vehicles is of utmost importance. Viral vectors are the most widely used delivery vehicles for gene therapy in vivo and in vitro due to their high transfection efficiency and stable transgene expression. With the development of nanotechnology, novel nanocarriers are gradually replacing viral vectors, emerging superior performance. This review mainly illuminates the current widely used gene therapy drugs, summarizes the viral vectors and non-viral vectors that deliver gene therapy drugs, and sums up the application of gene therapy to treat genetic diseases. Additionally, the challenges and opportunities of the field are discussed from the perspective of developing an effective nano-delivery system.

Ca2+ participating self-assembly of an apoferritin nanostructure for nucleic acid drug delivery.

One of the most encountered obstacles for utilizing nano-sized vehicles to implement the in vivo delivery of nucleic acid drugs (NADs) is the possible steric hindrance caused by their intrinsic size and charge. In this work, we added Ca2+ for the pH triggered self-assembly process of H-apoferritin (HFn), to neutralize negative charges and help siRNA condense during complexation and particle formation. As expected, the internalization efficiency of siRNA in HFn particle formation could be enhanced 1.65-fold, compared with that without incorporated Ca2+. Furthermore, the calcification that occurred within the cavity of HFn particles endows them with endosomal escape capability, which could explain their contribution to the demonstrated in vitro and in vivo gene silencing effect achieved by the internalized siRNA. Thus, this Ca2+ participating self-assembly process of a protein nanostructure would lead to advanced internalization efficiency for NAD therapy.

Food Protein-Based Nanodelivery Systems for Hydrophobic and Poorly Soluble Compounds.

The hydrophobicity of bioactive molecules poses a considerable problem in the pharmaceutical and the food industry. Using food-based protein nanocarriers is one promising way to deliver hydrophobic molecules. These types of protein possess many functional properties such as surface activity, water-binding capacity, emulsification, foaming, gelation, and antioxidant activity, as well as their incorporation in the food industry as ingredients. Besides, they express low toxicity, are less expensive compared to synthetic polymers, and are biodegradable. This review aims to give a brief overview of the recent studies done using food proteins as colloidal delivery systems for hydrophobic and poorly soluble compounds.

Soft and Condensed Nanoparticles and Nanoformulations for Cancer Drug Delivery and Repurpose.

Drug repurpose or reposition is recently recognized as a high-performance strategy for developing therapeutic agents for cancer treatment. This approach can significantly reduce the risk of failure, shorten R&D time, and minimize cost and regulatory obstacles. On the other hand, nanotechnology-based delivery systems are extensively investigated in cancer therapy due to their remarkable ability to overcome drug delivery challenges, enhance tumor specific targeting, and reduce toxic side effects. With increasing knowledge accumulated over the past decades, nanoparticle formulation and delivery have opened up a new avenue for repurposing drugs and demonstrated promising results in advanced cancer therapy. In this review, recent developments in nano-delivery and formulation systems based on soft (i.e., DNA nanocages, nanogels, and dendrimers) and condensed (i.e., noble metal nanoparticles and metal-organic frameworks) nanomaterials, as well as their theranostic applications in drug repurpose against cancer are summarized.

ROS-Mediated Apoptosis and Anticancer Effect Achieved by Artesunate and Auxiliary Fe(II) Released from Ferriferous Oxide-Containing Recombinant Apoferritin.

Reactive oxygen species (ROS)-mediated apoptosis is considered a crucial therapeutic mechanisms for artesunate (AS). As an Fe(II)-dependent drug, the anticancer effect of AS is often limited due to insufficient Fe(II) concentration in targeted cells. To overcome this problem, a recombinant apoferritin nanocarrier containing ferriferous oxide (M-HFn) is constructed to produce auxiliary exogenous Fe(II) when delivering AS to cancer cells. Here, the newly fabricated AS-loaded M-HFn nanoparticles (M-HFn@AS NPs) can significantly improve the tumor-specific targeting and intracellular uptake efficiency of AS in human cervical carcinoma cells. After being captured in the acidic cavity of endosomes, M-HFn@AS NPs can simultaneously release Fe(II) and allow AS to activate satisfactory ROS-mediated apoptosis. Furthermore, in vivo studies demonstrate that M-HFn@AS NPs can selectively accumulate in tumors to efficiently inhibit tumor growth. Thus, M-HFn@AS NPs are a promising system to enhance the therapeutic effect of Fe(II)-dependent drugs.

Promising Approach in the Treatment of Glaucoma Using Nanotechnology and Nanomedicine-Based Systems.

Glaucoma is considered a leading cause of blindness with the human eye being one of the body's most delicate organs. Ocular diseases encompass diverse diseases affecting the anterior and posterior ocular sections, respectively. The human eye's peculiar and exclusive anatomy and physiology continue to pose a significant obstacle to researchers and pharmacologists in the provision of efficient drug delivery. Though several traditional invasive and noninvasive eye therapies exist, including implants, eye drops, and injections, there are still significant complications that arise which may either be their low bioavailability or the grave ocular adverse effects experienced thereafter. On the other hand, new nanoscience technology and nanotechnology serve as a novel approach in ocular disease treatment. In order to interact specifically with ocular tissues and overcome ocular challenges, numerous active molecules have been modified to react with nanocarriers. In the general population of glaucoma patients, disease growth and advancement cannot be contained by decreasing intraocular pressure (IOP), hence a spiking in future research for novel drug delivery systems and target therapeutics. This review focuses on nanotechnology and its therapeutic and diagnostic prospects in ophthalmology, specifically glaucoma. Nanotechnology and nanomedicine history, the human eye anatomy, research frontiers in nanomedicine and nanotechnology, its imaging modal quality, diagnostic and surgical approach, and its possible application in glaucoma will all be further explored below. Particular focus will be on the efficiency and safety of this new therapy and its advances.

Pea-like nanocabins enable autonomous cruise and step-by-step drug pushing for deep tumor inhibition.

Pea-like nanocabins (HA@APT§DOX) were designed for deep tumor inhibition. The AS1411 aptamer (APT) constituted "core shelf" which guaranteed DOX "beans" could be embedded, while the outer HA acted as "pea shell" coating. During the circulation (primary orbit), HA@APT§DOX could autonomously cruise until leak through tumor vasculature. Upon tumor superficial site, the "pea shell" could be degraded by highly expressed hyaluronic acid enzymes (HAase) and peel-off, resulting in orbit changing of released APT§DOX to reach the deep tumor tissue. Furthermore, APT§DOX could be specifically uptaken into A549 tumor cells (secondary orbit). Finally, DOX was released under the acidic environment of lysosome, and delivered into nuclear (targeting orbit) to achieve drug pushing for deep tumor inhibition. More importantly, the in vivo imaging and anti-tumor effects evaluations showed that these nanocabins could effectively enhance drugs accumulation in tumor sites and inhibit tumor growth, with reduced systemic toxicity in 4T1 tumor-bearing mice.

Synthesis and compatibility evaluation of versatile mesoporous silica nanoparticles with red blood cells: an overview.

Protean mesoporous silica nanoparticles (MSNs) are propitious candidates over decades for nanoscale drug delivery systems due to their unique characteristics, including (but not limited to) changeable pore size, mesoporosity, high drug loading capacity, and biodegradability. MSNs have been drawing considerable attention as competent, safer and effective drug delivery vehicles day by day by their towering mechanical, chemical and thermal characteristics. Straightforward and easy steps are involved in the synthesis of MSNs at a relatively cheaper cost. This review reports Stober's synthesis, the first proposed synthesis procedure to prepare micron-sized, spherical MSNs, followed by other modifications later on done by scientists. To ensure the safety and compatibility of MSNs with biological systems, the hemocompatibility evaluation of MSNs using human red blood cells (RBCs) is a widely welcomed exercise. Though our main vision of this overview is to emphasize more on the hemocompatibility of MSNs to RBCs, we also brief about the synthesis and widespread applications of multifaceted MSNs. The strike of different parameters of MSNs plays a crucial role concerning the hemolytic activity of MSNs, which also has been discussed here. The inference is derived by centering some feasible measures that can be adopted to cut down or stop the hemolytic activity of MSNs in the future.