Nanotechnology

Nano magnetic liposomes-encapsulated parthenolide and glucose oxidase for ultra-efficient synergistic antitumor therapy

Abstract Multifunctional nanoplatforms yield extremely high synergistic therapeutic effects on the basis of low biological toxicity. Based on the unique tumor microenvironment (TME), a liposomes (Lips)-based multifunctional antitumor drug delivery system known as GOD-PTL-Lips@MNPs was synthesized for chemotherapy, chemodynamic therapy (CDT), starvation therapy, and magnetic targeting synergistic therapy. Evidence has suggested that parthenolide (PTL) can induce apoptosis and consume excessive glutathione (GSH), thereby increasing the efficacy of chemodynamic therapy. On the other hand, glucose oxidase (GOD) can consume intratumoral glucose, lower pH and increase the level of H 2 O 2 in the tumor tissue. Integrated Fe 3 O 4 magnetic nanoparticles (MNPs) containing Fe 2+ and Fe 3+ effectively catalyzes H 2 O 2 to a highly toxic hydroxyl radical (•OH) and provide magnetic targeting. During the course of in vitro and in vivo experiments, GOD-PTL-Lips@MNPs demonstrated remarkable synergistic antitumor efficacy. In particular, in mice receiving a 14 day treatment of GOD-PTL-Lips@MNPs, tumor growth was significantly inhibited, as compared with the control group. Moreover, toxicology study and histological examination demonstrated low biotoxicity of this novel therapeutic approach. In summary, our data suggests great antitumor potential for GOD-PTL-Lips@MNPs which could provide an alternative means of further improving the efficacy of anticancer therapies.

Moderating hypoxia and promoting immunogenic photodynamic therapy by HER-2 nanobody conjugate nanoparticles for ovarian cancer treatment

Abstract Photodynamic therapy (PDT) and immunotherapy have been often adopted for ovarian cancer therapy, yet their application is limited by the high recurrence rate and toxic side effects. Intriguingly, nanoparticles contribute to enhancing the performance of PDT. Here, we investigated the synthesis of HER-2-Nanobody (Nb)-conjugated human serum albumin (HSA) incorporated with chlorin (Ce6) and catalase (CAT) (Nb@HCC), and analyzed the synergic effect of Nb@HCC-mediated PDT and immunotherapy for SK-OV-3 tumors. The Ce6 and CAT were incorporated into HSA to construct the HCC nanoparticles. HER-2-Nanobody was the purified bacterial crude extract, and conjugated with HCC to prepare Nb@HCC via heterodisulfide. The effects of Nb@HCC with near infrared ray (NIR) irradiation on moderating hypoxia and hypoxia inducible factor-1 α (HIF-1 α ) expression were evaluated in the SK-OV-3 cells and tumor tissues. A SK-OV-3 tumor-bearing model was developed, where the synergistic effect of Nb@HCC-mediated PDT and anti-CTLA-4 therapy was investigated. Nb@HCC with a 660 nm laser irradiation could induce massive reactive oxygen species and trigger apoptosis in SK-OV-3 cells. Nb@HCC and PDT promoted danger-associated molecular patterns (DAMPs), which indicated immunogenic cell death and maturation of dendritic cells in the SK-OV-3 cells. Irradiated by NIR, Nb@HCC alleviated the hypoxia and decreased the expression of HIF-1 α . The Nb@HCC-mediated PDT and anti-CTLA-4 therapy synergically inhibited the progression of distant tumor, and induced T cell infiltration. Biosafety tests suggested that Nb@HCC would not cause damage to the major organs with less toxicity and side effects. To conclude, a combination of Nb@HCC-mediated PDT and anti-CTLA-4 therapy could inhibit the progression of distant tumor to attain remarkable therapeutic outcomes.

Multifunctional theranostic agents based on prussian blue nanoparticles for tumor targeted and MRI—guided photodynamic/photothermal combined treatment

Abstract The independence of photodynamic or photothermal modality create difficulties in the success of tumor therapy. In this current study, a multifunctional nanotheranostic agent of PDE-Ce6-HA was developed for tumor targeted and MRI-guided photodynamic/photothermal combined therapy (PDT/PTT). For this purpose, the near-infrared-absorbing nanoparticles of prussian blue were coated with polydopamine and successively conjugated with chlorin e6 (Ce6) for reactive oxygen species (ROS) generation. The resultant nanoparticles, denoted as PDE-Ce6, were then modified with hyaluronic acid (HA) through electrostatic interaction to yield the final therapeutic agent of PDE-Ce6-HA NPs. PDE-Ce6-HA NPs not only exhibited high colloid stability, good biocompatibility and suitable transverse relaxation rate (0.54 mM −1 s −1 ), but also high photothermal conversion efficiency (40.4%) and excellent ROS generation efficiency under NIR light irradiation. The confocal microscopy images demonstrated a selective uptake of PDE-Ce6-HA by CD44 overexpressed HeLa cells via HA-mediated endocytosis. Meanwhile, in vitro anti-cancer evaluation verified the significant photodynamic and photothermal combined effects of PDE-Ce6-HA on cancer cells. Moreover, PDE-Ce6-HA led to an increase of T 1 -MRI contrast in tumor site. Furthermore, in vivo anti-tumor evaluation proved that the PDE-Ce6-HA under both 808 and 670 nm laser showed significantly high tumor growth inhibition effects compared with individual PTT or PDT. Hence, PDE-Ce6-HA is applicable in tumor targeted and MRI-guided photodynamic/photothermal combined treatment.

Graphene oxide-based magnetic nanocomposites for the delivery of melittin to cervical cancer HeLa cells

Abstract Melittin (MEL), the primary active component of bee venom, has recently emerged as a promising cancer chemotherapeutic agent. However, the instability and rapid degradation of MEL is a significant challenge in practical therapeutic applications. In the present study, graphene oxide (GO)-based magnetic nanocomposites (PEG-GO-Fe 3 O 4 ) were prepared and adopted as the drug delivery vehicles of MEL, and the anticancer effects of PEG-GO-Fe 3 O 4 /MEL complexes on human cervical cancer HeLa cells were studied. PEG-GO-Fe 3 O 4 exhibited a series of unique physical and chemical properties resulting in multiple interactions with MEL, and ultimately the release of MEL. In vitro experiments showed that PEG-GO-Fe 3 O 4 /MEL not only distinctly enhanced the inhibition effect on HeLa cells, but also induced pore formation in the cell membrane that ultimately led to cell lysis. In this newly developed drug delivery system, PEGylated GO plays the role of a MEL protector while Fe 3 O 4 nanoparticles act as magnetic responders; therefore active MEL can be released over a long period of time (up to 72 h) and maintain its inhibition effect on HeLa cells.

Paclitaxel-loaded lignin particle encapsulated into electrospun PVA/PVP composite nanofiber for effective cervical cancer cell inhibition

Abstract Electrospun composite nanofibrous scaffolds have been regarded as a potential carrier for local drug delivery to prevent tumor recurrence. Herein, a model drug (paclitaxel) was creatively loaded into lignin nanoparticles (PLNPs) and then encapsulated into the polymer of poly (vinyl alcohol)/polyvinyl pyrrolidone which has been fabricated into a composite nanofibrous membrane (PVA/PVP-PLNPs) for use as a drug carrier using the electrospinning technique. The fabricated PVA/PVP-PLNPs membranes exhibited good particle distribution, mechanical properties, thermal stability and biocompatibility. In vitro experiments showed that combining lignin nanoparticles by electrospinning not only improved the drug release profile, but also enhanced the hydrophilicity of nanofibrous membranes which was beneficial to cell adhesion and proliferation. Cellular experiments demonstrated that PVA/PVP-2%PLNPs membrane showed good cell inhibition ability, and the cell survival rate was only 21% at day 7. It indicates that the as-prepared PVA/PVP-PLNPs composite nanofibers are promising candidates for local anticancer therapy.

Enhanced cytotoxicity of cisplatin-loaded Brij S100-alginate-taurine nanogels against HeLa cervical cancer cells

Abstract Water-insoluble anti-cancer drug delivery systems play a vital role in enhancing the effectiveness, stability, and selectivity of chemotherapeutic agents. By improving these properties, such systems offer better clinical outcomes, reduced systemic toxicity, and expanded therapeutic options, particularly for cancers that exhibit resistance to conventional treatments. In this context, nanogel-based delivery platforms constructed from Brij S100 grafted with alginate have demonstrated considerable promise. Two formulations were studied: Brij–Alg and Brij–Alg–Tau, the latter featuring surface modification of Brij–Alg nanogel particles with taurine molecules. These nanogels were used to encapsulate the anti-cancer drug cisplatin. The resulting drug-loaded nanogels exhibited desirable physicochemical characteristics, including optimal particle size, morphology, surface charge, and controlled drug release profiles suitable for targeted drug delivery applications. Importantly, both Brij–Alg and Brij–Alg-Tau nanogels displayed excellent biocompatibility, with minimal cytotoxicity toward fibroblast cells, indicating their safety for biological use. Cytotoxicity assay against the HeLa cervical cancer cell line revealed that Brij–Alg–Tau/CIS nanogels induced significantly greater cell death than both free CIS and Brij–Alg/CIS nanogels. The enhanced cytotoxicity is attributed to improved cellular uptake and sustained drug release enabled by the taurine-functionalized nanogel structure. These findings suggest that Brij–Alg–Tau nanogels are a promising vehicle for CIS delivery and hold strong potential for advancing cervical cancer therapy.

Design of fluorophore-loaded human serum albumin nanoparticles for specific targeting of NIH:OVCAR3 ovarian cancer cells

Abstract Nowadays, extensive research is being carried out to find innovative solutions for the development of stable, reproductible, and highly efficient fluorescent contrast agents with the ability of targeting specific cells, which can be further implemented for fluorescent-guided surgery in a real clinical setting. The present study is focused on the development of fluorescent dye-loaded protein nanoparticles (NPs) to overcome the drawbacks of the standard administration of free organic fluorophores, such as cytotoxicity, aqueousinstability, and rapid photo-degradation. Precisely, human serum albumin (HSA) NPs loaded with two different FDA approved dyes, namely indocyanine green (ICG) and fluorescein isothiocyanate (FITC), with a fluorescence response in the near-infrared and visible spectral domains, respectively, have been successfully designed. Even though the diameter of fluorescent HSA NPs is around 30 nm as proven by dynamic light scattering and transmission electron microscopy investigations, they present good loading efficiencies of almost 50% for ICG, and over 30% for FITC and a high particle yield of over 75%. Molecular docking simulations of ICG and FITC within the structure of HSA confirmed that the dyes were loaded inside the NPs, and docked in Site I (subdomain IIA) of the HSA molecule. After the confirmation of their high fluorescence photostability, the NPs were covalently conjugated with folic acid (HSA-FA NPs) in order to bind specifically to the folate receptor alpha (FRα) protein overexpressed on NIH:OVCAR3 ovarian cancer cells. Finally, fluorescence microscopy imaging investigations validate the improved internalization of folate targeted HSA&FITC NPs compared to cells treated with untargeted ones. Furthermore, TEM examinations of the distribution of HSA NPs into the NIH:OVCAR3 cells revealed anincreased number of NP-containing vesicles for the cells treated with HSA-FA NPs, compared to the cells exposed to untargeted HAS NPs, upholding the enhanced cellular uptake through FRα-mediated potocytosis.

Niosome-encapsulated balanocarpol: compound isolation, characterisation, and cytotoxicity evaluation against human breast and ovarian cancer cell lines

Abstract Natural products have been successfully used to treat various ailments since ancient times and currently several anticancer agents based on natural products are used as the main therapy to treat cancer patients, or as a complimentary treatment to chemotherapy or radiation. Balanocarpol, which is a promising natural product that has been isolated from Hopea dryobalanoides, has been studied as a potential anticancer agent but its application is limited due to its high toxicity, low water solubility, and poor bioavailability. Therefore, the aim of this study is to improve the characteristics of balanocarpol and increase its anticancer activity through its encapsulation in a bilayer structure of a lipid-based nanoparticle drug delivery system where the application of nanotechnology can help improve the limitations of balanocarpol. The compound was first extracted and isolated from H. dryobalanoides. Niosome nanoparticles composed of Span 80 (SP80) and cholesterol were formulated through an innovative microfluidic mixing method for the encapsulation and delivery of balanocarpol. The prepared particles were spherical, small, and uniform with an average particles size and polydispersity index ∼175 nm and 0.088, respectively. The encapsulation of balanocarpol into the SP80 niosomes resulted in an encapsulation efficiency of ∼40%. The niosomes formulation loaded with balanocarpol showed a superior anticancer effect over the free compound when tested in vitro on human ovarian carcinoma (A2780) and human breast carcinoma (ZR-75-1). This is the first study to report the use of SP80 niosomes for the successful encapsulation and delivery of balanocarpol into cancer cells.

Ultra-small lipid carriers with adjustable release profiles for synergistic treatment of drug-resistant ovarian cancer

Abstract Multidrug resistance has dramatically compromised the effectiveness of paclitaxel (PTX). The combined application of PTX and tetrandrine (TET) is a promising avenue in drug-resistant cancer therapy. However, poor drug release and limited intracellular drug accumulation greatly impede this combinational antitumor therapy. To address this problem, we successfully developed a tunable controlled release lipid platform (PT@usNLC) for coordinated drug delivery. The drug release rate of PT@usNLC can be tuned by varying the lipid ratio, which has potential to maximize the therapeutic effects of combined drugs. The TET release rate from PT@usNLC was faster than PTX, which could restore the sensitivity of tumor cells to PTX and exert a synergistic antitumor effect. The appropriate size of PT@usNLC could effectively increase the intracellular drug accumulation. Both in vitro and in vivo studies revealed that PT@usNLC significantly enhanced the therapeutic effect compared to conventional therapies. This study provides a new strategy for resistant ovarian cancer therapy.