Cervical Carcinoma HeLa Cells Research Articles

N-Doped graphene quantum dot@mesoporous silica nanoparticles modified with hyaluronic acid for fluorescent imaging of tumor cells and drug delivery.

The authors describe new bifunctional mesoporous silica nanoparticles (NPs) for specific targeting of tumor cells and for intracellular delivery of the cancer drug doxorubicin (DOX). Mesoporous silica nanoparticles (MSNPs) were coated with blue fluorescent N-graphene quantum dots, loaded with the drug DOX, and finally coated with hyaluronic acid (HA). Cellular uptake of the NPs with an architecture of the type HA-DOX-GQD@MSNPs enabled imaging of human cervical carcinoma (HeLa) cells via fluorescence microscopy. The cytotoxicity of the nanoparticles on HeLa cells was also assessed. The results suggest that the NPs are higher cytotoxicity effect and exert in living cell imaging ability. Compared to the majority of other drug nanocarrier systems, the one described here enables simultaneous DOX release and fluorescent monitoring. Graphical abstract Schematic of the bifunctional mesoporous silica nanoparticles were obtained via the Stöber method, along with the doxorubicin loaded and the hyaluronic acid capped. The sensor shows good specificity and significant cytotoxicity effect on Hela cells. (TEOS: tetraethyl orthosilicate; GQDs: graphene quantum dots; DOX: doxorubicin; HA: Hyaluronic acid).

Efficient inhibition of cervical cancer by dual drugs loaded in biodegradable thermosensitive hydrogel composites.

Background and PurposeWe aimed to explore the anti-tumor effect and mechanism of the combination of cisplatin (DDP)-containing thermosensitive hydrogel (PEG-PCL-PEG, or PECE) and paclitaxel (PTX)-loaded MPEG-PCL polymeric micelles called PDMP on human cervical carcinoma (HeLa) cell. In our previous studies, we found that PDMP in situ treatment of lung cancer will be liable to have potential in Lung cancer patients.ResultsCompared with other treatments, PDMP was most effective in prolonging survival time (P < 0.05), inhibiting tumor growth (P < 0.05), decreasing expression of CD133 (P < 0.05), CD31 (P < 0.05), and aldehyde dehydrogenase 1 (ALDH1) (P > 0.05), inducing G1 phase arrest (P < 0.05), increasing the apoptosis rate (P < 0.05), and in expressing ATM and γ-H2AX (P < 0.05).ConclusionsPDMP is regarded as a promising anti-tumor reactant, when it comes to the treatment of cervical carcinoma.Methodswe used a xenograft cervical cancer model to verify the anti-tumor activity of PDMP and to explore its mechanism of action. Mice were intratumorally administered with NS, PECE, PTX+DDP or PDMP. After two days of treatment, three mice per group were sacrificed and tumor tissue was harvested. Levels of histone H2AX phosphorylation (γ-H2AX) were determined by immunohistochemistry and ataxia telangiectasia mutated(ATM) protein levels were measured by western blot analysis. In addition, it would sacrifice each of group of three mice through 10 days’ treatment, what’s more, it would harvest tumor by virtue of flow cytometry and immunohistochemical analysis. It would like to use there maining mice to analyze tumor growth and survival. The remaining mice were analyzed for tumor growth and survival.

Radiation-Sensitive Dendrimer-Based Drug Delivery System.

Combination of chemotherapy and radiotherapy is used to enhance local drug delivery while reducing off‐target tissue effects. Anticancer drug doxorubicin (DOX) is loaded into l‐cysteine modified G4.5 dendrimer (GC/DOX) and released at different pH values in the presence and absence of γ‐radiation. Presence of γ‐radiation significantly improves DOX release from the GC/DOX under acidic pH conditions, suggesting that GC dendrimer is a radiation‐sensitive drug delivery system. GC/DOX is further evaluated by determining cytotoxicity in uterine cervical carcinoma HeLa cells. GC/DOX shows high affinity for cancer cells and effective drug release following an external stimulus (radiation exposure), whereas an in vivo zebrafish study confirms that l‐cysteine acts as a radiosensitizer. GC/DOX treatment combined with radiotherapy synergistically and successfully inhibits cancer cell growth.

Tapered Microfluidic for Continuous Micro-Object Separation Based on Hydrodynamic Principle.

Recent advances in microfluidic technologies have created a demand for a simple and efficient separation intended for various applications such as food industries, biological preparation, and medical diagnostic. In this paper, we report a tapered microfluidic device for passive continuous separation of microparticles by using hydrodynamic separation. By exploiting the hydrodynamic properties of the fluid flow and physical characteristics of micro particles, effective size based separation is demonstrated. The tapered microfluidic device has widening geometries with respect to specific taper angle which amplify the sedimentation effect experienced by particles of different sizes. A mixture of 3-μm and 10-μm polystyrene microbeads are successfully separated using 20° and 25° taper angles. The results obtained are in agreement with three-dimensional finite element simulation conducted using Abaqus 6.12. Moreover, the feasibility of this mechanism for biological separation is demonstrated by using polydisperse samples consists of 3-μm polystyrene microbeads and human epithelial cervical carcinoma (HeLa) cells. 98% of samples purity is recovered at outlet 1 and outlet 3 with flow rate of 0.5-3.0μl/min. Our device is interesting despite adopting passive separation approach. This method enables straightforward, label-free, and continuous separation of multiparticles in a stand-alone device without the need for bulky apparatus. Therefore, this device may become an enabling technology for point of care diagnosis tools and may hold potential for micrototal analysis system applications.

Synthesis and Anti-Proliferative Effects of Mono- and Bis-Purinomimetics Targeting Kinases.

A series of mono-pyrrolo[2,3-d]pyrimidines 4a–4k, unsymmetrical bis-purine isosteres 5a–5e and symmetrical bis-pyrrolo[2,3-d]pyrimidines 6a and 6b connected via di(1,2,3-triazolyl)phenyl linker were synthesized by click chemistry. Whereas mono- 4g and bis-pseudopurine 5e showed selective inhibitory activities on cervical carcinoma (HeLa) cells, bis-pyrrolo[2,3-d]pyrimidine 6b exhibited potent and selective anti-proliferative effect in the nanomolar range on pancreatic carcinoma (CFPAC-1) cells. Among these, compound 6b induced a significant reduction in the expression level of CDK9 (cyclin-dependent kinase 9)/cyclin T1 in CFPAC-1 cells concomitant with attenuation of proliferative signaling mediated by c-Raf (rapidly accelerated fibrosarcoma) and p38 MAP (mitogen-activated protein) kinases. Our findings encourage further development of novel structurally related analog of 6b to obtain more selective anticancer agent for treating pancreatic cancer.

Research on major antitumor active components in Zi-Cao-Cheng-Qi decoction based on hollow fiber cell fishing with high performance liquid chromatography

Hollow fiber cell fishing (HFCF) based on hepatoma HepG-2 cells, human renal tubular ACHN cells or human cervical carcinoma HeLa cells, coupled with high-performance liquid chromatography (HPLC), was developed and employed to research the major active components in Zi-Cao-Cheng-Qi decoction both in vitro and in vivo. The research showed that the active components, such as hesperidin, magnolol, honokiol, shikonin, emodin and β,β′-dimethylacrylshikonin were screened out by HFCF based on the cancer cells in vitro, furthermore they can be absorbed into blood and reach in the target organ, and some of the active components can be fished by the cells and maintain effective concentrations. Before application of HFCF with HPLC, cell growth state, cell survival rate, positive effect on screening results binding between active centers on the fiber and target components, repeatability of retention times and relative peak areas of the target analytes were analysed and investigated. In short, HFCF with HPLC is a simple, inexpensive, effective, and reliable method that can be used in researching active components from traditional Chinese medicine (TCM) and its formula both in vitro and in vivo, elucidating preliminarily the TCM characteristics of multiple components and multiple targets, laying a foundation for expounding the antitumor efficacy material basis in TCM.

Environmentally Responsive Dual-Targeting Nanoparticles: Improving Drug Accumulation in Cancer Cells as a Way of Preventing Anticancer Drug Efflux

Drug targeting and stimuli-responsive drug release are 2 active areas of cancer research and hold tremendous potential in the management of cancer drug resistance. In this study, I addressed this issue and focused on the synthesis and characterization of pH-responsive Fe3O4@SiO2(FITC)-BTN/folic acid/DOX multifunctional nanoparticles aiming to increase drug accumulation in malignancies with both dual active targeting and endosomal drug release properties. Dye-doped silica magnetic-fluorescent composite was constructed by a simple coprecipitation of Fe+2/Fe+3 salts followed by sol-gel formation and dual-targeting function was obtained by conjugating folate and biotin moieties on the silica surface of nanoparticles via an esterification reaction. Doxorubicin was then successfully attached on the amine-functionalized nanoparticles using a pH-sensitive Schiff-base formation. The physicochemical characterization of the structure was performed by dynamic light scattering, zeta potential measurement, X-ray diffraction, Fourier transform infrared spectroscopy, electron microscopy techniques, and an in vitro pH-dependent release study. Cellular uptake and cytotoxicity experiments demonstrated an enhanced intracellular delivery and reduction of cancer cell viability in the cervical carcinoma HeLa cell line. Furthermore, proapoptotic studies showed that the nanoparticles increased the apoptotic rates within the same cancer cells. The preliminary cell tests confirm the potential of these multifunctional nanoparticles against the development of drug resistance in cancer cells.

Photophysical, Cellular‐Uptake, and Bioimaging Studies of Luminescent Ruthenium(II)–Polypyridine Complexes Containing a d‐Fructose Pendant

Two luminescent ruthenium(II)–polypyridine complexes, appended with a d‐fructose unit, [Ru(N^N)2(bpy‐fructose)](PF6)2 [bpy‐fructose = 4‐(1‐deoxy‐d‐fructos‐1‐yl)aminocarbonyl‐4′‐methyl‐2,2′‐bipyridine; N^N = 4,7‐diphenyl‐1,10‐phenanthroline (Ph2‐phen) (1a) and 2,2′‐bipyridine (bpy) (2a)] and their d‐fructose‐free counterparts [Ru(N^N)2(bpy‐Et)](PF6)2 [bpy‐Et = 4‐(ethylaminocarbonyl)‐4′‐methyl‐2,2′‐bipyridine; N^N = Ph2‐phen (1b) and bpy (2b)] are synthesized and characterized. The photophysical properties, lipophilicity, cytotoxicity, and cellular uptake of the complexes are studied. Laser‐scanning confocal microscopy reveals that both complexes 1a and 1b display intense membrane staining toward human breast adenocarcinoma (MCF‐7) cells. However, while complex 1a retains its membrane‐staining characteristic when incubated with human cervical epithelioid carcinoma (HeLa) cells, complex 1b is localized in the mitochondria. Additionally, fructose‐dependent cellular‐uptake experiments suggest that complex 1a is transported into MCF‐7 cells through a glucose transporter (GLUT) mediated pathway.

Valproic Acid-Functionalized Cyclometalated Iridium(III) Complexes as Mitochondria-Targeting Anticancer Agents.

Valproic acid (VPA) is a short-chain, fatty acid type histone deacetylase inhibitor (HDACi), which can cause growth arrest and induce differentiation of transformed cells. Phosphorescent cyclometalated IrIII complexes have emerged as potential anticancer agents. By conjugation of VPA to IrIII complexes through an ester bond, VPA-functionalized cyclometalated iridium(III) complexes 1 a-3 a were designed and synthesized. These complexes display excellent two-photon properties, which are favorable for live-cell imaging. The ester bonds in 1 a-3 a can be hydrolyzed quickly by esterase and display similar inhibition of HDAC activity to VPA. Notably, 1 a-3 a can overcome cisplatin resistance effectively and are about 54.5-89.7 times more cytotoxic than cisplatin against cisplatin-resistant human lung carcinoma (A549R) cells. Mechanistic studies indicate that 1 a-3 a can penetrate into human cervical carcinoma (HeLa) cells quickly and efficiently, accumulate in mitochondria, and induce a series of cell-death-related events mediated by mitochondria. This study gives insights into the design and anticancer mechanisms of multifunctional anticancer agents.

Targeted delivery of mesoporous silica nanoparticles loaded monastrol into cancer cells: an in vitro study

Monastrol is a simple low molecular weight dihydropyrimidine-based kinesin Eg5 inhibitor. Its low cellular activity and its non-drug-like properties have impeded its further development. In a previous report, we have reported various topological parameters to improve the pharmacokinetic properties of monastrol. The purpose of this study is to determine the loading and release feasibility of poorly water-soluble monastrol into the synthesized mesoporous silica nanoparticles (MSNs). The synthesis of MSNs was attained by the ammonia-catalysed hydrolysis and condensation of TEOS in ethanol using polysorbate-80 as surfactant. These were characterized by BET surface area and pore size distribution analyses, SEM, XRD, UV and FTIR spectroscopy. The synthesized monastrol was successfully loaded on MSNPs and coated by hydrogels for successful controlled drug delivery. In vitro release studies are done by simple dialysis method. Monastrol-loaded MSNPs were tested on human cervical epithelial malignant carcinoma (HeLa) cell lines for studying their anticancer activity. Our presented system described a reliable method for targeted delivery of monastrol into the cancer cells in vitro.

Assessment of free radical scavenging and anti-proliferative activities of Tinospora cordifolia Miers (Willd)

BackgroundTinospora cordifolia (Guduchi or Amrita) is an important drug of Ayurvedic System of Medicine and found mention in various classical texts for the treatment of diseases such as jaundice, fever, diabetes, cancer and skin disease etc. In view of its traditional claims, antioxidant and anti-proliferative activities were evaluated in the present study.MethodsEthanol extract (TCE) and subsequent petroleum ether (TCP), dichloromethane (TCD), n-Butanol (TCB) and aqueous (TCA) fractions of were prepared from stems of T cordifolia. Total phenolic, flavonoid content and anti-oxidant activity was assessed by different methods. Anti-proliferative activity was assessed in cervical carcinoma (HeLa) cell lines by MTT and SRB assay.ResultsEthanol extract and n-butanol fractions shown to be superior in their scavenging activity in all the tested methods. n-butanol fractions shown antioxidant activity with an IC50 of 14.81 ± 0.53, 29.48 ± 2.23, 58.20 ± 0.70 and 21.17 ± 1.19 μg/mL by DPPH, ABTS, Nitric oxide and iron chelating activities respectively. Anti-proliferative activity results demonstrates that the TCD and ethanol extract of T cordifolia exhibits potent cytotoxic effect against HeLa with an IC50 of 54.23 ± 0.94 μg/mL and 101.26 ± 1.42 μg/mL respectively by MTT assay; and with an IC50 of 48.91 ± 0.33 μg/mL and 87.93 ± 0.85 μg/mL respectively by SRB assay.ConclusionThe outcomes of the present study support the fact that T Cordifolia is a promising source of antioxidant agent and propose its further investigation. Moreover, dichloromethane fraction of T cordifolia shown to be the most potent anti-proliferative fraction and further mechanistic and phytochemical investigations are under way to identify the active principles.

ID1056 Synthesis and biological evaluation of novel curcumin derivative with water-soluble phosphate group as potential antitumor agent

Background: Curcumin (diferuloylmethane) is the main natural active polyphenol from the rhizome of Curcuma longa (turmeric) and in others Curcuma spp. The main pharmacological effects include anti-tumor, anti-inflammatory, anti-oxidation, anti-fungal and anti-bacterial activities. However, the clinical application of curcumin is limited by its main drawbacks such as low solubility, poor bioavailability and rapid excretion from the body. In this study, the chemical modification approach was performed to improve the solubility of curcumin in water, at the same time increase the anti-tumor activity.&#x0D; Methods: The water-soluble compound (2-(curcumin-O-yl)ethyl dihydrophosphate, LH-42017) was synthesized by two classical reactions: O-alkylation with 2-bromoethanol to obtain mono-O-(2-hydroxyethyl)-curcumin, followed by esterification using phosphoryl chloride in water and pyridine. The chemical structure was confirmed by IR-, NMR-spectroscopies and mass-spectrometry. The anti-tumor activity of LH-42017 was assessed against hepatocellular carcinoma Hep-G2, human breast cancer MCF-7, human leukemia K562 and human cervical carcinoma HeLa cell lines based on the sulforhodamine B (SRB) assay.&#x0D; Results: LH-42017 was successfully synthesized from curcumin by overall yield of 28.43%. IC50 of original curcumin was 63.55, 90.88, 104.99 and 60.24 µM on Hep-G2, MCF-7, K562 and Hela, respectively. IC50 of LH-42017 was 36.82, 51.60, 60.80 and 26.14 µM on Hep-G2, MCF-7, K562 and Hela, respectively.&#x0D; Conclusion: The novel synthesized compound LH-42017 showed the antitumor activity in 1.7-2.3 times better than original curcumin. The water-soluble phosphate group plays an important role in development of natural curcumin as potential antitumor agent.

ID: 1040 Anticancer effects of natural products from animal and plant origin

For last couple of decades, natural products have served us well in combating different types of cancer. The main sources of these useful compounds are from both animal and plant origin. Here we will present anticancer ability of bee venom (BV) and apigenin (API) towards different types of cancer cells in vitro. BV from honey bees is a complex mixture of a variety of different active peptides while API is a natural flavonoid found in several dietary plant foods. Anticancer effect of whole BV was tested in human cervical carcinoma HeLa cells and their drug-resistant HeLa CK subline while anticancer effect of API was tested in human breast cancer MCF-7 and MDA MB-231 cells. Cytotoxicity of both compounds towards cancer cells was evaluated by MTT assay whereas type of cell death was analysed by differential staining using acridine orange/ethidium bromide and was further verified by Western blot analysis. BV displayed dose-dependent cytotoxicity against both cell lines tested with drug-resistant HeLa CK cells being more sensitive to BV than their parental cell lines. Similarly, API inhibited the growth of both cell lines in a dose-dependent manner with MCF-7 cells being more sensitive. Treatment with BV induced a necrotic type of cell death, as shown by characteristic morphological features, fast staining with ethidium bromide and a lack of cleavage of apoptotic marker poly (ADP-ribose) polymerase (PARP) on Western blot. On the contrary, cell treated with API showed apoptosis as a dominant type of cell death in both cell lines which was further verified by Western blot analysis detecting cleaved PARP. In view of accumulating evidence on anti-proliferative and pro-cell death activity, both tested compounds could be used in the development of future anticancer drugs. Undoubtedly, therapeutic applications of BV and API are promising, however further in vitro and in vivo studies are warranted to resolve precise mechanisms responsible for their anticancer properties

Lysine to arginine mutagenesis of chlorotoxin enhances its cellular uptake.

Chlorotoxin (CTX), a disulfide-rich peptide from the scorpion Leiurus quinquestriatus, has several promising biopharmaceutical properties, including preferential affinity for certain cancer cells, high serum stability, and cell penetration. These properties underpin its potential for use as a drug design scaffold, especially for the treatment of cancer; indeed, several analogs of CTX have reached clinical trials. Here, we focus on its ability to internalize into cells-a trait associated with a privileged subclass of peptides called cell-penetrating peptides-and whether it can be improved through conservative substitutions. Mutants of CTX were made using solid-phase peptide synthesis and internalization into human cervical carcinoma (HeLa) cells was monitored by fluorescence and confocal microscopy. CTX_M1 (ie, [K15R/K23R]CTX) and CTX_M2 (ie, [K15R/K23R/Y29W]CTX) mutants showed at least a twofold improvement in uptake compared to CTX. We further showed that these mutants internalize into HeLa cells largely via an energy-dependent mechanism. Importantly, the mutants have high stability, remaining intact in serum for over 24h; thus, retaining the characteristic stability of their parent peptide. Overall, we have shown that simple conservative substitutions can enhance the cellular uptake of CTX, suggesting that such type of mutations might be useful for improving uptake of other peptide toxins.

Evaluation of in vitro and in vivo therapeutic antitumor efficacy of transduction of polo-like kinase 1 and heat shock transcription factor 1 small interfering RNA.

Mitotic progression is regulated by the phosphorylation of heat shock transcription factor 1 (HSF1) by polo-like kinase 1 (PLK1); however, this interaction is often deregulated in tumors. High expression levels of PLK1 and HSF1 have been observed in various types of human cancer. In the present study, it was investigated whether small interfering (si)RNA against PLK1 or HSF1 could suppress tumor growth in vitro and in vivo. In vitro transfection of PLK1 and HSF1 siRNA into PKL1- and HSF1-positive human breast tumor MDA-MB-231 and human cervical carcinoma HeLa cells inhibited cell growth via suppression of PLK1 and HSF1 mRNA expression, respectively. However, the transfection of PLK1 or HSF1 siRNA did not significantly affect the cytotoxicity of doxorubicin in HeLa cells. Furthermore, injection of PKL1 or HSF1 siRNA into mice with liver HeLa metastasis suppressed tumor growth. From these findings, PLK1 and HSF1 may be considered to be promising targets for antitumor therapy.

Acid-degradable gadolinium-based nanoscale coordination polymer: A potential platform for targeted drug delivery and potential magnetic resonance imaging

During conventional chemotherapy for cancer, nonspecific drug distribution, which causes serious side effects in normal tissues, is a serious limitation. Thus, it is desirable to develop a tumor or intracellular microenvironment-responsive nanosystem for targeted and on-demand drug release. In the present study, we engineered an intelligent pH-activatable nanosystem, in which a gadolinium-doxorubicin-loaded nanoscale coordination polymer (Gd-Dox NCPs) was the core and hyaluronic acid was the targeting shell. Taking advantage of CD44 receptor-mediated recognition, the nanoparticles were internalized selectively into human cervical carcinoma (HeLa) cells, and trapped within acidic compartments where the fluorescence of Dox recovered, along with the acid dismantling of the Gd NCPs, allowing real-time monitoring of drug release. In vitro experiments also showed that the Gd NCPs present enhanced T1 signals after acid-triggered degradation, suggesting their potential use as contrast agents for magnetic resonance imaging. Such nanocarriers, which feature high biodegradation, selective targeting ability, and rapid response to stimulus, demonstrated enhanced therapeutic efficacy in targeted cancer cells and “turned on” T1 signals in vitro, showing great promise for diagnosis and treatment.

Hydrothermal synthesis of N-doped carbon dots for selective fluorescent sensing and cellular imaging of cobalt(II)

Strongly blue fluorescent N-doped carbon dots (CDs) were synthesized by using citric acid (CA) as the carbon source and diethylenetriamine (DETA) as the nitrogen source using a one-step hydrothermal method. Several synthetic parameters, including the molar ratios of initial starting materials, the temperature and time of hydrothermal reaction, were investigated and optimized. The range and average value of the diameters of the resultant CDs were 1.2–4.0 nm and 2.3 nm, respectively. The synthesized CDs display fluorescence with excitation/emission maxima of 391/438 nm and a quantum yield of 58%. Fluorescence is quenched by Co(II) ions, and this effect was exploited to design a method for determination of Co(II) in water and to image it in living HeLa (cervical carcinoma) cells. The limit of detection and linear range of Co2+ using the synthesized CDs as fluorescence probe are 0.4 μmol·L−1 and 0–90 μmol·L−1, respectively. Due to the selective and sensitive response of Co2+, the CDs possess potential applications in biological labeling for the demands such as monitoring the distribution of vitamin B-12 or other cobalt-containing medicines in cells or organisms.

Normonanchocidins G and H, New Pentacyclic Guanidine Alkaloids from the Far-Eastern Marine Sponge Monanchora pulchra

Two new pentacyclic guanidine alkaloids, normonanchocidins G (1) and H (2) containing an unusual ω-2-hydroxy fatty acid moiety were isolated from the Far-Eastern marine sponge Monanchora pulchra. The structures of 1 and 2 were determined by 1D- and 2D-NMR spectroscopic and mass spectrometric data interpretation. Compounds 1 and 2 exhibit potent cytotoxic activities against human leukemia THP-1, HL-60 cells, human cervical epithelioid carcinoma HeLa cells and also have high impact on ability of HeLa cells to migrate.

Identifying the cellular location of brain cytoplasmic 200 RNA using an RNA-recognizing antibody.

Brain cytoplasmic 200 RNA (BC200 RNA) is a neuron-specific non-coding RNA, implicated in the inhibition of local synaptodendritic protein synthesis, and is highly expressed in some cancer cells. Although BC200 RNA has been shown to inhibit translation in vitro, the cellular location of this inhibition is unknown. In this study, we used a BC200 RNA-recognizing antibody to identify the cellular locations of BC200 RNA in HeLa cervical carcinoma cells. We observed punctate signals in both the cytoplasm and nucleus, and further discovered that BC200 RNA co-localized with the p-body decapping enzyme, DCP1A, and the heterogeneous nuclear ribonucleoprotein E2 (hnRNP E2). The latter is a known BC200 RNA-binding partner protein and a constituent of p-bodies. This suggests that BC200 RNA is localized to p-bodies via hnRNP E2.

Nucleation and Assembly of Silica into Protein-Based Nanocomposites as Effective Anticancer Drug Carriers Using Self-Assembled Silk Protein Nanostructures as Biotemplates.

Bombyx mori (B. mori) silk fibroin and sericin can act as a great candidate in delivering drugs or other bioactive substances. Silica also has a great application in the field of drug delivery. To the best of our knowledge, there has been no report on the design of a nanocomposite made of silk protein and silica for drug delivery. Here, for the first time, we used B. mori silk fibroin (SF) and sericin (SS), self-assembled into nanospheres and nanofibers in situ in the aqueous solution, respectively, as a biotemplate to regulate the nucleation and self-assembly of silica for designing anticancer drug delivery. SF and SS mediated the nucleation and assembly of silica into monodispersed nanospheres (termed Si/SF) and nanofibers (termed Si/SS), respectively. The size and topography of the silica assemblies were dependent on the concentration of SF or SS as well as reaction conditions. Both Si/SF nanospheres and Si/SS nanofibers showed a high loading capability and sustained release profile of an anticancer drug, doxorubicin (DOX), in vitro. Si/SF nanospheres were found to be efficiently internalized in human cervical carcinoma (HeLa) cells and accumulate around the cell nuclei. Si/SS nanofibers could only adhere to the surface of the cancer cells. This indicates that DOX-loaded Si/SF nanospheres and Si/SS nanofibers are more effective in cancer therapy than free DOX. Our results suggest that the self-assembled Si/SF spheres and Si/SS nanofibers are potential effective anticancer drug carriers.