Sericin Nanoparticles Research Articles

Multifunctional sericin-based biomineralized nanoplatforms with immunomodulatory and angio/osteo-genic activity for accelerated bone regeneration in periodontitis

Periodontitis is a chronic inflammation caused by dental plaque. It is characterized by the accumulation of excessive reactive oxygen species (ROS) and inflammatory mediators in the periodontal area. This affects the function of host cells, activates osteoclasts, and destroys periodontal tissue. Treatments such as local debridement or antibiotic therapy for ameliorating the overactive inflammatory microenvironment and repairing periodontal tissues are challenging. This paper reports multifunctional nanoplatforms (Se-CuSrHA@EGCG) based on sericin with ROS-scavenging, immunomodulatory, angiogenic, and osteogenic capabilities. The natural protein sericin, derived from silk cocoons, is used in water/oil emulsification and cross-linking processes to create sericin nanoparticles (Se NPs). Numerous binding sites are present on the surface of Se NPs. Ion-doped hydroxyapatite nanoparticles (Se-CuSrHA NPs) can be constructed using the force between positive and negative charges. After mineralization, an antioxidant coating is formed on the surface using polyethyleneimine (PEI)/epigallocatechin gallate (EGCG). Research conducted both in vitro and in vivo demonstrates that Se-CuSrHA@EGCG NPs can efficiently scavenge ROS, regulate macrophage polarization, increase the secretion of anti-inflammatory cytokines, and balance the immune microenvironment. In addition, Se-CuSrHA@EGCG stimulates angiogenesis, inhibits osteoclasts, and accelerates periodontal tissue repair. Therefore, this is a preferable strategy to accelerate bone regeneration in patients with periodontitis.

Therapeutic potential of silkworm sericin in wound healing applications.

Chronic wounds are characterised by an imbalance between pro and anti-inflammatory signals, which result in permanent inflammation and delayed re-epithelialization, consequently hindering wound healing. They are associated with bacterial infections, tissue hypoxia, local ischemia, reduced vascularization, and MMP-9 upregulation. The global prevalence of chronic wounds has been estimated at 40 million in the adult population, with an alarming annual growth rate of 6.6%, making it an increasingly significant clinical problem. Sericin is a natural hydrophilic protein obtained from the silkworm cocoon. Due to its biocompatibility, biodegradability, non-immunogenicity, and oxidation resistance, coupled with its excellent affinity for target biomolecules, it holds great potential in wound healing applications. The silk industry discards 50,000 tonnes of sericin annually, making it a readily available material. Sericin increases cell union sites and promotes cell proliferation in fibroblasts and keratinocytes, thanks to its cytoprotective and mitogenic effects. Additionally, it stimulates macrophages to release more therapeutic cytokines, thus improving vascularization. This review focuses on the biological properties of sericin that contribute towards enhanced wound healing process and its mechanism of interaction with important biological targets involved in wound healing. Emphasis is placed on diverse wound dressing products that are sericin based and the utilisation of nanotechnology to design sericin nanoparticles that aid in chronic wound management.

DIFUCOSIN: DIclofenac sodium salt loaded FUCOidan-SericIN nanoparticles for the management of chronic inflammatory diseases

The current investigation emphasizes the use of fucoidan and sericin as dual-role biomaterials for obtaining novel nanohybrid systems for the delivery of diclofenac sodium (DS) and the potential treatment of chronic inflammatory diseases. The innovative formulations containing 4 mg/ml of fucoidan and 3 mg/ml of sericin showed an average diameter of about 200 nm, a low polydispersity index (0.17) and a negative surface charge. The hybrid nanosystems demonstrated high stability at various pHs and temperatures, as well as in both saline and glucose solutions. The Rose Bengal assay evidenced that fucoidan is the primary modulator of relative surface hydrophobicity with a two-fold increase of this parameter when compared to sericin nanoparticles. The interaction between the drug and the nanohybrids was confirmed through FT-IR analysis. Moreover, the release profile of DS from the colloidal systems showed a prolonged and constant drug leakage over time both at pH 5 and 7. The DS-loaded nanohybrids (DIFUCOSIN) induced a significant decrease of IL-6 and IL-1β with respect to the active compound in human chondrocytes evidencing a synergistic action of the individual components of nanosystems and the drug and demonstrating the potential application of the proposed nanomedicine for the treatment of inflammation.

Enhancing Cisplatin Efficacy with Low Toxicity in Solid Breast Cancer Cells Using pH-Charge-Reversal Sericin-Based Nanocarriers: Development, Characterization, and In Vitro Biological Assessment.

Platinum-based chemotherapeutic agents are widely employed in cancer treatment because of their effectiveness in targeting DNA. However, this indiscriminate action often affects both cancerous and normal cells, leading to severe side effects and highlighting the need for innovative approaches in achieving precise drug delivery. Nanotechnology presents a promising avenue for addressing these challenges. Protein-based nanocarriers exhibit promising capabilities in the realm of cancer drug delivery with silk sericin nanoparticles standing out as a leading contender. This investigation focuses on creating a sericin-based nanocarrier (SNC) featuring surface charge reversal designed to effectively transport cisplatin (Cispt-SNC) into MCF-7 breast cancer cells. Utilizing AutoDock4.2, our molecular docking analyses identified key amino acids and revealed distinctive conformational clusters, providing insights into the drug-protein interaction landscape and highlighting the potential of sericin as a carrier for controlled drug release. The careful optimization and fabrication of sericin as the carrier material were achieved through flash nanoprecipitation, a straightforward and reproducible method that is devoid of intricate equipment. The physicochemical properties of SNCs and Cispt-SNCs, particularly concerning size, surface charge, and morphology, were evaluated using dynamic light scattering (DLS) and scanning electron microscopy (SEM). Chemical and conformational analyses of the nanocarriers were conducted using Fourier-transform infrared spectroscopy (FTIR) and circular dichroism (CD), and elemental composition analysis was performed through energy-dispersive X-ray spectroscopy (EDX). This approach aimed to achieve the smallest nanoparticle size for Cispt-SNCs (180 nm) and high drug encapsulation efficiency (84%) at an optimal sericin concentration of 0.1% (w/v), maintaining a negative net charge at a physiological pH (7.4). Cellular uptake and cytotoxicity were investigated in MCF-7 breast cancer cells. SNCs demonstrated stability and exhibited a pH-dependent drug release behavior, aligning with the mildly acidic tumor microenvironment (pH 6.0-7.0). Efficient cellular uptake of Cispt-SNC, along with DNA fragmentation and chromatin condensation, was found at pH 6, leading to cell apoptosis. These results collectively indicate the potential of SNCs for achieving controlled drug release in a tumor-specific context. Our in vitro studies reveal the cytotoxicity of both cisplatin and Cispt-SNCs on MCF-7 cells. Cisplatin significantly reduced cell viability at 10 μM concentration (IC50), and the unique combination of sericin and cisplatin showcased enhanced cell viability compared to cisplatin alone, suggesting that controlled drug release is indicated by a gradient decrease in cell viability and highlighting SNCs as promising carriers. The study underscores the promise of protein-based nanocarriers in advancing targeted drug delivery for cancer therapy.

Characterization and functional properties of novel nanocomposite sericin-based films incorporated with sericin nanoparticles

Sericin is an interesting protein that can be formed into sericin films for biomedical and food applications. Moreover, sericin can be prepared as sericin nanoparticles (SNs) and incorporated to enhance the film barrier properties. The SNs had a size of 407 nm, as verified by dynamic light scattering. To improve the mechanical properties of sericin films, pectin was added at different ratios of sericin:pectin (w:w) (3:0, 3:1, 3:2, and 3:3). Additionally, various amounts of SNs (0, 5, and 10%) were incorporated to form nanocomposite sericin-based films. The addition of pectin and SNs led to lower solubility and higher water vapor permeability than sericin film alone. The Fourier-transform infrared results showed that the interaction between sericin and pectin molecules increased the tensile strength of the films. Furthermore, the differential scanning calorimetry results indicated that adding pectin to sericin films increased the melting temperature, resulting in improved thermal stability of the composite films. However, higher pectin content reduced the total phenolic content and antioxidant activity. Nonetheless, SNs incorporation helped increase the antioxidant activity of composite films. Thus, the nanocomposite sericin-based films could be an alternative for food packaging materials or biomedical applications.

Sericin/crocetin micro/nanoparticles for nucleus pulposus cells regeneration: An "active" drug delivery system.

Introduction: Initiation and progression of intervertebral disk degeneration are linked to oxidative stress, with reactive oxygen species being a key factor. Therefore, as a potentially novel approach able to regenerate the damaged intervertebral disk, this work aimed to prepare an "active per sé" drug delivery system by combining sericin and crocetin: both are bioactive compounds with antioxidant, anti-inflammatory, immunomodulant and regenerative properties. Methods: In detail, sericin nanoparticles were prepared using crocetin as a cross-linker; then, the nanoparticle dispersions were dried by spray drying as it is (NP), with an excess of sericin (NPS) or crocin/crocetin (NPMix), obtaining three microparticle formulations. Results and Discussion: Before drying, the nanoparticles were nanometric (about 250nm), with a negative surface charge, and appeared spherical and smooth. Following the drying process, spherical and smooth microparticles were obtained, with a mean diameter of about 1.7-2.30μm. NPMix was the most active in antioxidant and anti-tyrosinase activities, likely due to the excess of crocin/crocetin, while NPS had the best anti-elastase activity, likely due to sericin in excess. Furthermore, all the formulations could prevent oxidative stress damage on nucleus pulposus cells, with NPMix being the best. Overall, the intrinsic anti-tyrosinase and anti-elastase activities and the ability to protect from oxidative stress-induced damages justify future investigations of these "active per sé" formulations in treating or preventing intervertebral disk degeneration.

Topical application of zein-silk sericin nanoparticles loaded with curcumin for improved therapy of dermatitis

Atopic dermatitis is characterized by leukocyte migration into the skin dermis and typically driven by excessive chemokine production at the site of inflammation. Conventional topical formulations such as gels, creams, and ointments are insufficient for this treatment because of low penetration of drug molecules into the targeted skin tissues. Herein, using a simple, green, sustainable strategy, we have developed novel primary zein nanoparticles embedded in curcumin (Cur) and coated with silk sericin (ZHSCs) for the topical delivery of Cur to penetrate into the dermis and exercise anti-dermatitis effects on the lesion with minimal side-effects. Transdermal delivery experiments and porcine skin fluorescence imaging indicated that ZHSCs facilitate the penetration of Cur across the epidermis layer of skin to reach deep-seated sites. Notably, ZHSCs = 1:0.25 (zein-to-silk sericin mass ratios of 1:0.25) markedly elevated the skin permeability and cumulative turnover of Cur transferred, which were provided a greater than a 3.8-fold increase relative to free Cur. The special nanoparticles of ZHS = 1:0.25 possessed the deepest localization depth and experience a transition of the particle structure and core-shell separation after penetrating into the dermis of skin. In a cell model of dermatitis induced by tumor necrosis factor α/interferon γ co-stimulation, compared with free Cur, Cur-loaded ZHS nanoparticles down-regulated the generation of inflammatory cytokines and chemokines in keratinocytes through suppression of the nuclear translocation of NF-κBp65 and hence exerted an anti-dermatitis effect. This strategy may provide new avenues and direction for the demanding issues of valid topical delivery systems.

Preparation of Moisturizing Lotion Containing Silkworm (Bombyx mori L.) Sericin Nanoparticles

Sericin as one of two main proteins in silkworm (Bombyx mori L.) cocoons was found to have the ability to increase skin moisture in cosmetics. The objective of this study was to determine the optimal formula of sericin nanoparticle lotion and the effectiveness of sericin nanoparticle lotion. The formation of sericin nanoparticles was mainly carried out by mixing and stirring mechanism using urea as a crosslinking agent. Temperature and stirring speed were fixed, while stirring duration were varied. Optimal sericin nanoparticles with the average particle size of 701 nm were obtained at 800 rpm stirring for 30 minutes at room temperature. Sericin nanoparticles lotion was then formulated with 5% and 10% sericin nanoparticles. Results showed that lotion containing 5% and 10% sericin nanoparticles significantly increase skin moisture.Keywords: moisturizer, lotion, silkworm, sericin, nanoparticles

In Vitro Interaction of Doxorubicin-Loaded Silk Sericin Nanocarriers with MCF-7 Breast Cancer Cells Leads to DNA Damage.

In this paper, Bombyx mori silk sericin nanocarriers with a very low size range were obtained by nanoprecipitation. Sericin nanoparticles were loaded with doxorubicin, and they were considered a promising tool for breast cancer therapy. The chemistry, structure, morphology, and size distribution of nanocarriers were investigated by Fourier transformed infrared spectroscopy (FTIR–ATR), scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and dynamic light scattering (DLS). Morphological investigation and DLS showed the formation of sericin nanoparticles in the 25–40 nm range. FTIR chemical characterization showed specific interactions of protein–doxorubicin–enzymes with a high influence on the drug delivery process and release behavior. The biological investigation via breast cancer cell line revealed a high activity of nanocarriers in cancer cells by inducing significant DNA damage.

Crocetin as New Cross-Linker for Bioactive Sericin Nanoparticles.

The nose-to-brain delivery route is used to bypass the blood–brain barrier and deliver drugs directly into the brain. Over the years, significant signs of progress have been made in developing nano-drug delivery systems to address the very low drug transfer levels seen with conventional formulations (e.g., nasal solutions). In this paper, sericin nanoparticles were prepared using crocetin as a new bioactive natural cross-linker (NPc) and compared to sericin nanoparticles prepared with glutaraldehyde (NPg). The mean diameter of NPc and NPg was about 248 and 225 nm, respectively, and suitable for nose-to-brain delivery. The morphological investigation revealed that NPc are spherical-like particles with a smooth surface, whereas NPg seem small and rough. NPc remained stable at 4 °C for 28 days, and when freeze-dried with 0.1% w/v of trehalose, the aggregation was prevented. The use of crocetin as a natural cross-linker significantly improved the in vitro ROS-scavenging ability of NPc with respect to NPg. Both formulations were cytocompatible at all the concentrations tested on human fibroblasts and Caco-2 cells and protected them against oxidative stress damage. In detail, for NPc, the concentration of 400 µg/mL resulted in the most promising to maintain the cell metabolic activity of fibroblasts higher than 90%. Overall, the results reported in this paper support the employment of NPc as a nose-to-brain drug delivery system, as the brain targeting of antioxidants is a potential tool for the therapy of neurological diseases.

Curcumin loaded sericin nanoparticles: Assessment for biomedical application

The present study is aimed at formulating Genipin crossed curcumin loaded sericin NPs (Cur-SNPs) for the biomedical application in terms of anti-inflammatory and antioxidant potential. Cur-SNPs were prepared by employing modified desolvation method and crosslinking using genipin (Gn) and optimization for particle size, drug entrapment and loading. The optimized curcumin loaded sericin NPs (Opt-Cur-SNPs) exhibited particle size (263±3.5 nm), entrapment efficiency (85.7 ± 1.20%), drug loading (47.0 ± 1.23%) and zeta potential (-25.65 mV). The in-vitro drug release data revealed that 72.0 ± 2.3% and 83.1 ± 1.0% curcumin release over a span of 60 h in simulated gastric fluid and colonic pH. In-vivo antioxidant activity and anti-inflammatory activity showed significant results (p<0.05 and p<0.01) in comparison to control rats. The pharmacokinetic study revealed that the formulation holds better bioavailability and sustained release as compared to parent API. The present study confirms the hypothesis, that the Cur-SNPs can be used for biomedical application.

Arginine induces protein self-assembly into nanofibers for triggering osteogenic differentiation of stem cells.

Although silk proteins are considered promising in building a scaffold for tissue engineering, one of the silk proteins, Bombyx mori silk sericin (BS), has limited processability in producing nanofibrous scaffolds because its surface charge anisotropy promotes gelation instead. To overcome this daunting challenge, we developed a mild and simple procedure for assembling BS into nanofibers and nanofibrous scaffolds. Briefly, arginine was added to the aqueous BS solution to reduce the negative charge of BS, thereby inducing BS to self-assemble into nanofibers in the solution. Circular dichroism (CD) and Fourier transform infrared (FT-IR) spectra showed that arginine promoted the formation of β-sheet conformation in BS and increased its thermal stability. Furthermore, the arginine-induced BS nanofiber solution could be casted into scaffolds made of abundant network-like nanofibrous structures. The BS scaffolds promoted cell adhesion and growth and stimulated osteogenic differentiation of the bone marrow mesenchymal stem cells (BMSCs) in the absence of differentiation inducers in culture media. Our study presents a new strategy for assembling proteins into osteogenic nanofibrous scaffolds for inducing stem cell differentiation in regenerative medicine.

Polyphenols-Loaded Sericin Self-Assembling Nanoparticles: A Slow-Release for Regeneration by Tissue-Resident Mesenchymal Stem/Stromal Cells.

Mesenchymal stem/stromal cells (MSCs) are a therapeutic target to promote tissue regeneration, mainly when oxidative stress-mediated damage is involved in disease pathogenesis. Here, slow-release silk sericin nanoparticles (SNPs) loaded with natural antioxidant polyphenols were developed to sustain regeneration by tissue-resident MSCs. SNPs were prepared by exploiting a self-assembly method with poloxamer and were loaded with proanthocyanidins (P), quercetin (Q) or epigallocatechin gallate (E). SNPs, with a diameter less than 150 nm, were able to encapsulate both hydrophilic (P and E) and hydrophobic (Q) drugs. A slow and controlled release was obtained from SNPs for all the actives in PBS, while in EtOH, Q and E showed a burst release but P did not. Kinetic models revealed lower diffusion of P than other biomolecules, probably due to the higher steric hindrance of P. The in vitro anti-oxidant, anti-elastase and anti-tyrosinase properties of SNPs were assessed: loading the P and E into SNPs preserved the in vitro biological activities whereas for Q, the anti-elastase activity was strongly improved. Moreover, all formulations promoted MSC metabolic activity over 72 h. Finally, SNPs exhibited a strong ability to protect MSCs from oxidative stress, which supports their potential use for regenerative purposes mediated by tissue-resident MSCs.

Green synthesis of poly-L-lysine-coated sericin nanoparticles and their molecular size-dependent antibacterial activity

Investigating the role of molecular size and interfacial potential dependent antimicrobial propensity of nanoparticles (NPs) against bacteria is the important goal for secure usage of NPs to any living systems. In this study, crude silk sericin protein of Antheraea mylitta cocoon was fractionated into three different molecular size-ranges fractions such as fraction-1 (50−300 kDa), fraction-2 (30−50 kDa) and fraction-3 (10−30 kDa), and used to prepare crude sericin nanoparticles (CRSNPs), as well as fraction specific negative surface potential nanoparticles : n-SNP1, n-SNP2 and n-SNP3, respectively. SNPs were coated with poly-l-lysine to make the surface potential positive (p-SNPs) and confirmed through UV–vis spectroscopy, FTIR, zeta sizer and zeta potential measurement. The shape and sizes of all SNPs were determined by electron microscopy and found spherical in shape having diameter ranging from 110−165 nm (CRSNPs), 66−85 nm (SNP1), 33−49 nm (SNP2) and 14−24 nm (SNP3) for n-SNPs and p-SNPs, respectively. Evaluation of antibacterial activity using different concentrations (50, 100, 200 μg/mL) of all these SNPs showed significantly more activity of p-SNPs than n-SNPs against Staphylococcus aureus and Escherichia coli. Among these, SNP2 showed the strongest antibacterial activity followed by SNP3, SNP1 and CRSNPs. Relatively higher amounts of reactive oxygen species (ROS) generation were observed after treatment of bacteria with p-SNP2 (50 μg/mL) which is non-toxic to human cells. FE-SEM analysis showed more disruption of bacterial cell membrane after treatment with p-SNPs than n-SNPs. All these data suggested that molecular size and interfacial potential of SNPs enhance ROS generation to exert their antibacterial activity.

Green approaches for preparation and comparative analysis of three different molecular sizes of multifunctional sericin nanoparticles

Green approaches for preparation and comparative analysis of three different molecular sizes of multifunctional sericin nanoparticles

Formulation and Evaluation of Novel Sericin Nanoparticles for Buccal Delivery of Antihypertensive Drug

The aim of this study is to prepare and evaluate sericin nanoparticles (NPs) of Verapamil Hcl which are finally formulated as buccal gel. It was envisaged to formulate the nanoparticles with gelatine, sericin and genipin. Nanoparticles incorporated gel was successfully prepared by using carbopol 934. Nanoparticles were prepared by dessolvation followed by crosslinking. Various parameters like drug content, viscosity, pH, spreadability and drug release were used to obtain the optimized formulation. The sericin nanoparticles incorporated gel shows better fast release as compare to API. The obtained results like drug content, % drug release, buccal permeation study confirmed the potential of nanoparticles as good carrier for buccal administration. The optimised sericin nanoparticles range between 100-400 nm with a zeta potential of 29.91mv showing good stability. Later, we proved our hypothesis through In vitro studies for pharmacokinetics, where we found that NPs had better bioavailability than API. NPs showed protective action and maintained normal tissue architecture. We concluded that nanoparticle form of verapamil had better bioavailability and good pharmacological actions, which might be beneficial for future formulation design perspective.

Efficiency of resveratrol-loaded sericin nanoparticles: Promising bionanocarriers for drug delivery

Sericin protein nanoparticles are a biocompatible, bio-viable class of nanocarriers gaining prominence in drug delivery system. This research aimed to investigate the suitability fabrication of silk protein (SP) nanoparticles for loading with resveratrol (RSV) via a solventless precipitation technique. The addition of 0.5% (w/v) pluronic surfactant proved optimal for SP nanoparticle fabrication, with obtained nanoparticles being spherical, mono-dispersed and having mean size of approximately 200–400 nm. All exhibited negative surface charges, the extent of which being dependent on the SP concentration, and were non-toxic to normal skin fibroblasts (CRL-2522). Loading of RSV, a promising which poorly soluble multi-targeted anti-oxidative and anti-inflammatory natural polyphenol, into SP nanoparticles proved feasible, with encapsulation levels of 71–75% for 0.6% and 1.0% (w/v) nanoparticle formulations, respectively. Resveratrol-loaded SP nanoparticles strongly inhibited growth of colorectal adenocarcinoma (Caco-2) cells although proved non-cytotoxic to skin fibroblasts, as indicated by cell viability assays. Cellular internalization of SP nanoparticles proved facile and dependent on incubation time; transfection of these carriers, in vitro results indicating sustained release of RSV (over 72 h), and drug solubility enhancements on encapsulation highlight their potential in therapeutic and pharmaceutical applications. Thus, SP nanoparticles is a promising approach to be potential bio-nanocarrier for drug delivery system.

Novel genipin crosslinked atorvastatin loaded sericin nanoparticles for their enhanced antihyperlipidemic activity

The objective of this study was to demonstrate the therapeutic as well as biopolymer like characteristics of naturally occurring sericin protein for development of nanoparticulate system of atorvastatin (Atr) to improve therapeutic effect and to reduce toxicity. The sericin encapsulated atorvastatin nanoparticles (Seri-Atr NPs) were prepared by desolvation method utilizing genipin (Gn) as a natural and nontoxic crosslinker. The optimized NPs exhibited small particle size (166±0.30nm), high entrapment efficiency (91±0.69%) and uniform spherical shape with sustained release profile. Moreover, the results of pharmacokinetic studies indicated an increase in AUC0−∞ of NPs (1189.74±52.3hng/ml) compared with Atr (501.84±66hng/ml). The cellular uptake of NPs suggested an interaction of negatively charged particles with the cell surface and considerable reduction in systemic toxicity. Histopathology studies also demonstrated the therapeutic potential of sericin and cytocompatibility. Hence, genipin crosslinked sericin based nanoparticles represents a promising nanoplatform for improved therapeutic efficiency of Atr.

Design and Fabrication of Multifunctional Sericin Nanoparticles for Tumor Targeting and pH-Responsive Subcellular Delivery of Cancer Chemotherapy Drugs.

The severe cytotoxicity of cancer chemotherapy drugs limits their clinical applications. Various protein-based nanoparticles with good biocompatibility have been developed for chemotherapy drug delivery in hope of reducing drugs' side effects. Sericin, a natural protein from silk, has no immunogenicity and possesses diverse bioactivities that have prompted sericin's application studies. However, the potential of sericin as a multifunctional nanoscale vehicle for cancer therapy have not been fully explored. Here we report the successful fabrication and characterization of folate-conjugated sericin nanoparticles with cancer-targeting capability for pH-responsive release of doxorubicin (these nanoparticles are termed "FA-SND"). DOX is covalently linked to sericin through pH-sensitive hydrazone bonds that render a pH-triggered release property. The hydrophobicity of DOX and the hydrophilicity of sericin promote the self-assembly of sericin-DOX (SND) nanoconjugates. Folate (FA) is then covalently grafted to SND nanoconjugates as a binding unit for actively targeting cancer cells that overexpress folate receptors. Our characterization study shows that FA-SND nanoparticles exhibit negative surface charges that would reduce nonspecific clearance by circulation. These nanoparticles possess good cytotoxicity and hemocompatibiliy. Acidic environment (pH 5.0) triggers effective DOX release from FA-SND, 5-fold higher than does a neutral condition (pH 7.4). Further, FA-SND nanoparticles specifically target folate-receptor-rich KB cells, and endocytosed into lysosomes, an acidic organelle. The acidic microenvironment of lysosomes promotes a rapid release of DOX to nuclei, producing cancer specific chemo-cytotoxicity. Thus, FA-mediated cancer targeting and lysosomal-acidity promoting DOX release, two sequentially-occurring cellular events triggered by the designed components of FA-SND, form the basis for FA-SND to achieve its localized and intracellular chemo-cytotoxicity. Together, this study suggests that these FA-SND nanoparticles may be a potentially effective carrier particularly useful for delivering hydrophobic chemotherapeutic agents for treating cancers with high-level expression of folate receptors.

Fabrication of sericin nanoparticles for controlled gene delivery

Protein based nanoparticles are functionally efficient for delivery of biomolecules and can be eliminated from the body due to their biodegradable nature.