Search

ABSTRACT: α-Lactalbumin (α-lac), a natural food-sourced protein, exhibits high biocompatibility as delivery systems for small bioactive molecules or RNA. However, their potential clinical application as a delivery system is greatly limited due to the lack of targeting to desired tissues, such as tumors. Here, a delivery system/nanocarrier of nanotube (NT) was fabricated by the self-assembly of peptides hydrolyzed from α-lac. Among the loading of anti-tumor agents of doxorubicin (Dox) and siRNA, NTs were conjugated with the tLyp-1 peptide to specifically target the neuropilin 1 receptor, which exists on the membrane of MDA-MB-231 cancer cells. The micromorphology of NTs was not affected during the processes of loading and targeting modification. Additionally, no significant changes in the size and zeta potential of the tLyp-1/NTs/Dox/siRNA nanocarrier were observed when stored in phosphate buffered saline for 7 days, indicating outstanding stability. Moreover, both the cellular uptake efficiency and tumor accumulation effects of NTs on MDA-MB-231 breast cancer cells were significantly improved after modification with tLyp-1. The relative viability of MDA-MB-231 cells was decreased by 70.1% in vitro after treatment with tLyp-1/NTs/Dox/siRNA (5 μg/mL Dox). Finally, a synergistic anticancer effect of Dox and siRNA co-loaded in tLyp-1/NTs was achieved in the anticancer treatment of MDA-MB-231 tumor-bearing mice. These findings indicate that food-sourced protein α‑lac nanocarriers could be used for the co-delivery of bioactive molecules and RNA, achieving synergistic and efficient therapeutic effects.

Optimizing the delivery and penetration of nano-sized drugs within liver cancer sites, along with remodeling the tumor microenvironment, is crucial for enhancing the efficacy of chemotherapeutic agents. For this study, a platelet (PLT)-mediated nanodrug delivery system (DASA+ATO@PLT) was developed to improve the effectiveness of chemotherapy. This system delivers nano-sized dasatinib and atovaquone specifically to liver tumor sites and facilitates intra-tumoral permeation upon release. Through JC-1, immunohistochemistry, and DNA damage analyses, the therapeutic effect of DASA+ATO@PLT was assessed. In vitro simulation and intravital imaging were carried out to determine the accumulation of dasatinib and atovaquone in liver tumor sites. The experiment demonstrated the accumulation of dasatinib and atovaquone in tumor sites, followed by deep permeation in the tumor microenvironment with the assistance of PLTs, while simultaneously revealing the ability of DASA+ATO@PLT to remodel the liver cancer microenvironment (overcoming hypoxia) and enhance chemotherapeutic efficacy. This system utilizes the natural tumor recognition ability of PLTs and enhances the chemo-immunotherapeutic effect through targeted delivery of nano-chemotherapeutic drugs to the tumor, resulting in effective accumulation and infiltration. The PLT-mediated nanodrug delivery system serves as a “Trojan horse” to carry therapeutic drugs as cargo and deliver them to target cells, leading to favorable outcomes.

Oleic acid (OA) is a kind of monounsaturated omega-3 fatty acid that abounds in plants and animals which can induce apoptosis and has broad-spectrum inhibitory activity against a variety of tumor cell lines. However, OA is quite insoluble and thus inconvenient to be efficiently delivered in vivo. In this work, OA was fabricated into nanoparticles to generate OA elastic nanoparticles (OA-ENPs) with a particle size of 185.6 nm and good stability in various physiological media. OA-ENPs alone achieved a high tumor inhibition rate of 60.3% without significant side effect. More surprisingly, the resultant OA-ENPs displayed dose-dependent tumor targetability. Low dose of OA-ENPs (10 mg/kg) mainly distributed in the liver after intravenous injection, while high dose of OA-ENPs mainly distributed in tumor. At the high dose of 90 mg/kg, OA-ENPs accumulation in tumor reached nearly twice as that in the liver. Here we provide a simple but effective way to achieve excellent tumor targetability without the need of any surface modification of nanoparticles.

The conventional concept of using nanocarriers to deliver chemotherapeutic drugs has advanced to accommodate additional diagnostic capability. Nanotheranostic agents (NTA), combining both treatment and diagnostic tools, are an ideal example of engineering-health integration for cancer management. Owing to the diverse materials used to construct NTAs, their safety, effectiveness, and diagnostic accuracy could vary substantially. This systematic review consolidated current NTAs incorporating 5-fluorouracil and elucidated their toxicity, anticancer efficacy, and imaging capability. Medline and Embase databases were searched up to March 18, 2022. The search, selection, and extraction were performed by the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines to ensure completeness and reproducibility. Original research papers involving 5-fluorouracil in the preparation of nanoparticles which reported their efficacy, toxicity, and diagnostic capability in animal cancer models were recruited. The quality of included studies was assessed using the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) checklist. Nine studies were eligible for the systematic review. There was no significant toxicity reported based on animal weight and organ histology. Complete tumor remission was observed in several animal models using chemo-thermal ablation with NTAs, proving the enhancement of 5-fluorouracil efficacy. In terms of imaging performance, the time to achieve maximum tumor image intensity correlates with the presence of targeting ligand on NTAs. The NTAs, which are composed of tumor-targeting ligands, hold promises for further development. Based on the input of current NTA research on cancer, this review proposed a checklist of parameters to recommend researchers for their future NTA testing, especially in animal cancer studies.Systematic Review Registration: website, identifier registration number.

Vitamin E Poly(ethylene glycol) monoplatinum ester (TPGS) nanoparticles have attracted much attention in recent years for overcome multidrug resistance. Herein, a well-defined folic acid (FA)-conjugated and disulfide bond-linked polymer (FA-SS-TPGS) was synthesized. These polymer nanoparticles were utilized as theranostic agents for tumor-targeted magnetic resonance imaging (MRI) and chemotherapy. By loading doxorubicin (DOX) and superparamagnetic iron oxide (SPIO) particles into TPGS nanoparticles, FA-SS-TPGS@DOX/SPIO nanoparticles are obtained. In vitro drug release studies revealed that under a reducing environment in the presence of glutathione (GSH), approximately 100% of the doxorubicin (DOX) was released from the disulfide bond-linked theranostic nanoparticles within 24 h. DOX and SPIO were efficiently delivered into HepG2-ADM cells due to the folate receptor-mediated endocytosis process of the nanoparticles. Additionally, the presence of glutathione (GSH) triggered the cleaving of the disulfide bonds, further facilitating the delivery of DOX and SPIO into the cells. Furthermore, the FA-SS-TPGS @DOX-SPIO nanoparticles exhibited strong MRI contrast enhancement properties. In conclusion, FA-SS-TPGS@DOX/SPIO are potential nanoparticles for tumor-targeted MRI and chemotherapy, which can also overcome multidrug resistance.

Polymeric micelles (PMs) have made significant progress in drug delivery applications. A robust core–shell structure, kinetic stability and the inherent ability to solubilize hydrophobic drugs are the highlights of PMs. This review presents the recent advances and understandings of PMs with a focus on the latest drug delivery applications. The types, methods of preparation and characterization of PMs are described along with their applications in oral, parenteral, transdermal, intranasal and other drug delivery systems. The applications of PMs for tumor-targeted delivery have been provided special attention. The safety, quality and stability of PMs in relation to drug delivery are also provided. In addition, advanced polymeric systems and special PMs are also reviewed. The in vitro and in vivo stability assessment of PMs and recent understandings in this area are provided. The patented PMs and clinical trials on PMs for drug delivery applications are considered indicators of their tremendous future applications. Overall, PMs can help overcome many unresolved issues in drug delivery.

β-cyclodextrin(βCD)-based star polymers have attracted much interest because of their unique structures and potential biomedical and biological applications. Herein, a well-defined folic acid (FA)-conjugated and disulfide bond-linked star polymer ((FA-Dex-SS)-βCD-(PCL)14) was synthesized via a couple reaction between βCD-based 14 arms poly(ε-caprolactone) (βCD-(PCL)14) and disulfide-containing α-alkyne dextran (alkyne-SS-Dex), and acted as theranostic nanoparticles for tumor-targeted MRI and chemotherapy. Theranostic nanoparticles were obtained by loading doxorubicin (DOX), and superparamagnetic iron oxide (SPIO) particles were loaded into the star polymer nanoparticles to obtain ((FA-Dex-SS)-βCD-(PCL)14@DOX-SPIO) theranostic nanoparticles. In vitro drug release studies showed that approximately 100% of the DOX was released from disulfide bond-linked theranostic nanoparticles within 24 h under a reducing environment in the presence of 10.0 mM GSH. DOX and SPIO could be delivered into HepG2 cells efficiently, owing to the folate receptor-mediated endocytosis process of the nanoparticles and glutathione (GSH), which triggered disulfide-bonds cleaving. Moreover, (FA-Dex-SS)-βCD-(PCL)14@DOX-SPIO showed strong MRI contrast enhancement properties. In conclusion, folic acid-decorated reduction-sensitive star polymeric nanoparticles are a potential theranostic nanoparticle candidate for tumor-targeted MRI and chemotherapy.

Osteosarcoma (OSA) is a type of bone cancer that begins in the cells that form bones. OSA is a rare mesenchymal bone neoplasm derived from mesenchymal stem cells. Genome disorganization, chromosomal modifications, deregulation of tumor suppressor genes, and DNA repair defects are the factors most responsible for OSA development. Despite significant advances in the diagnosing and treatment of OSA, patients’ overall survival has not improved within the last twenty years. Lately, advances in modern nanotechnology have spurred development in OSA management and offered several advantages to overcome the drawbacks of conventional therapies. This technology has allowed the practical design of nanoscale devices combined with numerous functional molecules, including tumor-specific ligands, antibodies, anti-cancer drugs, and imaging probes. Thanks to their small sizes, desirable drug encapsulation efficiency, and good bioavailability, functionalized nanomaterials have found wide-spread applications for combating OSA progression. This review invokes the possible utility of engineered nanomaterials in OSA diagnosis and treatment, motivating the researchers to seek new strategies for tackling the challenges associated with it.