Surfactant like peptides for targeted gene delivery to cancer cells.

Surfactant like peptides (SLPs) are a class of amphiphilic peptides widely used for drug delivery and tissue engineering. However, there are very few reports on their application for gene delivery. The current study was aimed at development of two new SLPs, named (IA)4K and (IG)4K, for selective delivery of antisense oligodeoxynucleotides (ODNs) and small interfering RNA (siRNA) to cancer cells. The peptides were synthesized by Fmoc solid phase synthesis. Their complexation with nucleic acids was studied by gel electrophoresis and DLS. The transfection efficiency of the peptides was assessed in HCT 116 colorectal cancer cells and human dermal fibroblasts (HDFs) using high content microscopy. The cytotoxicity of the peptides was assessed by standard MTT test. The interaction of the peptides with model membranes was studied using CD spectroscopy. Both SLPs delivered siRNA and ODNs to HCT 116 colorectal cancer cells with high transfection efficiency which was comparable to the commercial lipid-based transfection reagents, but with higher selectivity for HCT 116 compared to HDFs. Moreover, both peptides exhibited very low cytotoxicity even at high concentrations and long exposure time. The current study provides more insights into the structural features of SLPs required for nucleic acid complexation and delivery and can therefore serve as a guide for the rational design of new SLPs for selective gene delivery to cancer cells to minimize the adverse effects in healthy tissues.

Silk Fibroin as a Functional Biomaterial for Tissue Engineering.

Tissue engineering (TE) is the approach to combine cells with scaffold materials and appropriate growth factors to regenerate or replace damaged or degenerated tissue or organs. The scaffold material as a template for tissue formation plays the most important role in TE. Among scaffold materials, silk fibroin (SF), a natural protein with outstanding mechanical properties, biodegradability, biocompatibility, and bioresorbability has attracted significant attention for TE applications. SF is commonly dissolved into an aqueous solution and can be easily reconstructed into different material formats, including films, mats, hydrogels, and sponges via various fabrication techniques. These include spin coating, electrospinning, freeze drying, physical, and chemical crosslinking techniques. Furthermore, to facilitate fabrication of more complex SF-based scaffolds with high precision techniques including micro-patterning and bio-printing have recently been explored. This review introduces the physicochemical and mechanical properties of SF and looks into a range of SF-based scaffolds that have been recently developed. The typical TE applications of SF-based scaffolds including bone, cartilage, ligament, tendon, skin, wound healing, and tympanic membrane, will be highlighted and discussed, followed by future prospects and challenges needing to be addressed.

Recent Advances in Microfluidics for the Preparation of Drug and Gene Delivery Systems.

Drug delivery systems (DDSs) have great potential for improving the treatment of several diseases, especially microbial infections and cancers. However, the formulation procedures of DDSs remain challenging, especially at the nanoscale. Reducing batch-to-batch variation and enhancing production rate are some of the essential requirements for accelerating the translation of DDSs from a small scale to an industrial level. Microfluidic technologies have emerged as an alternative to the conventional bench methods to address these issues. By providing precise control over the fluid flows and rapid mixing, microfluidic systems can be used to fabricate and engineer different types of DDSs with specific properties for efficient delivery of a wide range of drugs and genetic materials. This review discusses the principles of controlled rapid mixing that have been employed in different microfluidic strategies for producing DDSs. Moreover, the impact of the microfluidic device design and parameters on the type and properties of DDS formulations was assessed, and recent applications in drug and gene delivery were also considered.

A Review of Curcumin and Its Derivatives as Anticancer Agents.

Cancer is the second leading cause of death in the world and one of the major public health problems. Despite the great advances in cancer therapy, the incidence and mortality rates of cancer remain high. Therefore, the quest for more efficient and less toxic cancer treatment strategies is still at the forefront of current research. Curcumin, the active ingredient of the Curcuma longa plant, has received great attention over the past two decades as an antioxidant, anti-inflammatory, and anticancer agent. In this review, a summary of the medicinal chemistry and pharmacology of curcumin and its derivatives in regard to anticancer activity, their main mechanisms of action, and cellular targets has been provided based on the literature data from the experimental and clinical evaluation of curcumin in cancer cell lines, animal models, and human subjects. In addition, the recent advances in the drug delivery systems for curcumin delivery to cancer cells have been highlighted.

Microfluidic formulation of food additives-loaded nanoparticles for antioxidation.

Browning has many important implications with nutrition and the shelf life of foods. Mitigating browning is of particular interest in food chemistry. The addition of antioxidants has been a common strategy to extend shelf life of drug and food products. In this work, we report a microfluidic technology for encapsulation of three common food additives (potassium metathionite (PMS), curcumin (CCM), and ß-carotene (ß-Car)) into nano-formulations using low-cost and readily available materials such as shellac. The food additives encapsulated nanoparticles provide a microenvironment that can prevent oxidation during daily storage. The results showed that the produced nanoparticles had a narrow size distribution with an average size of around 100 nm, were stable at conventional storage conditions (4 ºC) for 18 weeks, and had sustained release ability at 37 ºC, pH= 7.8, 160 rpm. In addition, further experiments showed that the formulation of hydrophobic additives, such as CCM and ß-Car did not only improve their bioavailability but also allowed for the encapsulation of a combination of ingredients. In addition, the antioxidants loaded nanoparticles demonstrated good biocompatibility, low toxicity to human cells. The longer release time of encapsulated food additives increases shelf life of foods and enhances consumer purchase preferences, which not only saves costs but also reduces waste. In summary, this study shows that such antioxidant-loaded nanoparticles provide a promising strategy in extending the shelf life of food products.

Microfluidic formulation of anticancer peptide loaded ZIF-8 nanoparticles for the treatment of breast cancer.

Anticancer peptides (ACPs) are promising antitumor drugs owning to their great cancer cell targeting and anticancer effects as well as low drug resistance. However, many of the ACPs have non-specific toxicity and can be easily degraded by the enzymes after administration. Therefore, drug delivery systems (DDSs) are required to shield these peptides from degradation and induce targeted delivery. In this paper, a high performance microfluidic device was used to fabricate the zeolitic imidazolate framework (ZIF-8) encapsulating an ACP (At3) recently developed by our group. The microfluidic device allowed for efficient and rapid mixing to generate ACP loaded nanoparticles (NPs) with controllable properties at high production rate (120 mL/min) and high encapsulation efficiency. The ZIF-8 NPs synthesised by microfluidic processing showed lower polydispersity index (PDI) than the conventional method, demonstrating an improved size uniformity. Encapsulating At3 into the ZIF-8 (At3@ZIF-8) significantly reduced the hemolytic effect and provided a pH-controlled release of At3 peptide. At3@ZIF-8 showed higher anticancer effect than the unloaded peptide at the same concentration due to the enhanced cell uptake by the ZIF-8 NPs. The NPs were able to inhibit the growth of the multicellular tumour spheroids (MCTSs) and damage the mitochondrial membrane of the MCF-7 breast cancer cells. In vivo experiments demonstrated that the At3@ZIF-8 NPs inhibited the growth of MCF-7 tumours in nude mice without changing the biochemical properties of the blood or the histopathological properties of vital organs. Therefore, the development of At3 loaded NPs provides an alternative approach in ACP delivery which can broaden the application of ACP-based cancer therapy.

Microfluidic fabrication of photo-responsive Ansamitocin P-3 loaded liposomes for the treatment of breast cancer.

Ansamitocin P-3 (AP-3) is a promising anticancer agent. However, its low solubility has limited its biomedical applications. The preparation of liposomal formulations for the delivery of low solubility drugs using the microfluidic platform has attracted increasing attention in the pharmaceutical industry. In addition, photodynamic therapy (PDT) is a non-invasive and efficient strategy for the treatment of cancers, making photodynamic liposomes one of the most promising drug delivery systems (DDSs). In this study, a recently developed microfluidic device (swirl mixer) was used for the manufacturing of temperature-sensitive liposomes (TSL) that can be activated by near-infrared stimulation for the treatment of breast cancer. Changing the processing parameters of the microfluidic system allowed for optimizing the properties of the produced liposomes (e.g., particle size and size distribution). For the first time, the anticancer drug AP-3 and the photosensitizer indocyanine green (ICG) were encapsulated into TSL (AP-3/ICG@TSL) during microfluidic processing. The results show that AP-3/ICG@TSL are biocompatible and can significantly reduce the toxicity of AP-3 to normal tissues. After infrared laser irradiation, the heat generated from ICG not only resulted in the cancer cell toxicity, but also facilitated the release of AP-3 in tumor cells. AP-3/ICG@TSL with infrared laser irradiation was found to be able to significantly inhibit the growth of MCF-7 multicellular tumor spheroids (MCTSs) in vitro and MCF-7 tumors subcutaneously inoculated in nude mice as an in vivo model. In addition, it also showed no signs of damage to other organs. The current results demonstrated that the AP-3/ICG@TSL fabricated using the microfluidic swirl mixer is a promising DDS for breast cancer therapy.

Peptide-functionalised magnetic silk nanoparticles produced by a swirl mixer for enhanced anticancer activity of ASC-J9.

Silk fibroin is an FDA approved biopolymer for clinical applications with great potential in nanomedicine. However, silk-based nanoformulations are still facing several challenges in processing and drug delivery efficiency (such as reproducibility and targetability), especially in cancer therapy. To address these challenges, robust and controllable production methods are required for generating nanocarriers with desired properties. This study aimed to develop a novel method for the production of peptide-functionalized magnetic silk nanoparticles with higher selectivity for cancer cells for targeted delivery of the hydrophobic anticancer agent ASC-J9. A new microfluidic device with a swirl mixer was designed to fabricate magnetic silk nanoparticles (MSNP) with desired size and narrow size distribution. The surface of MSNPs was functionalized with a cationic amphiphilic anticancer peptide, G(IIKK)3I-NH2 (G3), to enhance their selectivity towards cancer cells. The G3-MSNPs increased the cellular uptake and anticancer activity of G3 in HCT 116 colorectal cancer cells compared to free G3. Moreover, the G3-MSNPs exhibited considerably higher cellular uptake and cytotoxicity in HCT 116 colorectal cancer cells compared to normal cells (HDFs). Encapsulating ASC-J9 in G3-MSNPs resulted in augmented anticancer activity compared to free ASC-J9 and non-functionalized ASC-J9 loaded MSNPs within its biological half-life. Hence, functionalizing MSNPs with G3 enabled targeted delivery of ASC-J9 to cancer cells and enhanced its anticancer effect. Functionalization of nanoparticles with anticancer peptides could be regarded as a new strategy for targeted delivery and enhanced efficiency of anticancer drugs. Furthermore, the microfluidic device introduced in this paper offers a robust and reproducible method for fabrication of small sized homogenous nanoparticles.

Rationally designed short cationic α-helical peptides with selective anticancer activity.

HYPOTHESIS: Naturally derived or synthetic anticancer peptides (ACPs) have emerged as a new generation of anticancer agents with higher selectivity for cancer cells and less propensity for drug resistance. Despite the structural diversity of ACPs, α-helix is the most common secondary structure among them. Herein we report the development of a new library of short cationic amphiphilic α-helical ACPs with selective cytotoxicity against colorectal and cervical cancer. EXPERIMENTS: The peptides had a general formula C(XXYY)3 with C representing amino acid cysteine (providing a -SH group for molecular conjugation), X representing hydrophobic amino acids (isoleucine (I) or leucine (L)), and Y representing cationic amino acids (arginine (R) or lysine (K)). Two variants of the peptides were synthesized by adding additional Isoleucine residues to the C-terminal and replacing the N-terminal cysteine with LC-propargylglycine (LC-G) to investigate the effect of N-terminal and C-terminal variation on the anticancer activity. The structure and physicochemical properties of the peptides were determined by RP-HPLC, LC-MS and CD spectroscopy. The cytotoxicity of the peptides in different cell lines was assessed by MTT test, cell proliferation assay and mitochondrial damage assay. The mechanism of cell selectivity of the peptides was investigated by studying their interfacial behaviour at the air/water and lipid/water interface using Langmuir trough. FINDINGS: The peptides consisting of K residues in their hydrophilic domains exhibited more selective anticancer activity whereas the peptides containing R exhibited strong toxicity in normal cells. The anticancer activity of the peptides was a function of their helical content and their hydrophobicity. Therefore, the addition of two I residues at C-terminal enhanced the anticancer activity of the peptides by increasing their hydrophobicity and their helical content. These two variants also exhibited strong anticancer activity against colorectal cancer multicellular tumour spheroids (MCTS). The higher toxicity of the peptides in cancer cells compared to normal cells was the result of higher penetration into the negatively charged cancer cell membranes, leading to higher cellular uptake, and their cytotoxic effect was mainly exerted by damaging the mitochondrial membranes leading to apoptosis. The results from this study provide a basis for rational design of new α-helical ACPs with enhanced anticancer activity and selectivity.

Correlation between the secondary structure and surface activity of ß-sheet forming cationic amphiphilic peptides and their anticancer activity.

Cancer is one of the main causes of death worldwide. The current cancer treatment strategies often lack selectivity for cancer cells resulting in dose-limiting adverse effects and reduced quality of life. Recently, anticancer peptides (ACPs) have emerged as an alternative treatment with higher selectivity, less adverse effects, and lower propensity for drug resistance. However, most of the current studies on the ACPs are focused on α-helical ACPs and there is lack of systematic studies on ß-sheet forming ACPs. Herein we report the development of a new series of rationally designed short cationic amphiphilic ß-sheet forming ACPs and their structure activity relationship. The peptides had the general formula (XY1XY2)3, with X representing hydrophobic amino acids (isoleucine (I) or leucine (L)), Y1 and Y2 representing cationic amino acids (arginine (R) or lysine (K)). The cytotoxicity of the designed ACPs in HCT 116 colorectal cancer, HeLa cervical cancer and human dermal fibroblast (HDF) cells was assessed by MTT test. The physicochemical properties of the peptides were characterized by various techniques including RP-HPLC, LC-MS, and Circular Dichroism (CD) spectroscopy. The surface activity of the peptides at the air-water interface and their interaction with the lipid monolayers as models for cell membranes were studied by Langmuir trough. The peptides consisting of I with R and K had selective anticancer activity while the combination of L and R diminished the anticancer activity of the peptides but rendered them more toxic to HDFs. The anticancer activity of the peptides was directed by their surface activity (amphiphilicity) and their secondary structure in hydrophobic surfaces including cancer cell membranes. The selectivity of the peptides for cancer cells was a result of their higher penetration into cancer cell membranes compared to normal cell membranes. The peptides exerted their anticancer activity by disrupting the mitochondrial membranes and eventually apoptosis. The results presented in this study provide an insight into the structure-activity relationship of this class of ACPs which can be employed as guidance to design new ACPs with improved anticancer activity and lower toxicity against normal cells.

Optimization of large-scale manufacturing of biopolymeric and lipid nanoparticles using microfluidic swirl mixers.

Nanoparticles (NPs) have great potential as efficient drug delivery systems (DDSs) that have been widely used in cancer therapy and vaccines especially in the past decade. The rise in demand from the pharmaceutical industry drives the growth of the global NPs market. However, complex production processes have hindered the market growth. Therefore, the development of advanced preparation techniques such as microfluidics is required to improve productivity and controllability. In this study, we present a novel microfluidic design (swirl mixer) that helps accelerating the translation of many DDSs from laboratory to clinical application. The new swirl mixer provides high production rate, reproducibility, and precise control of particle size with low polydispersity index (PDI). To assess the performance of the swirl mixer, two different types of nanoformulations were used: silk nanoparticles (SNPs) and lipid nanoparticles (LNPs). The microfluidic device produced NPs efficiently with high productivity and allowed for tuning the mean size and size distribution by changing multiple processing parameters.

Novel microfluidic swirl mixers for scalable formulation of curcumin loaded liposomes for cancer therapy.

Liposomes have been widely used in nanomedicine for the delivery of hydrophobic and hydrophilic anticancer agents. The most common applications of these formulations are vaccines and anticancer formulations (e.g., mRNA, small molecule drugs). However, large-scale production with precise control of size and size distribution of the lipid-based drug delivery systems (DDSs) is one of the major challenges in the pharmaceutical industry. In this study, we used newly designed microfluidic swirl mixers with simple 3D mixing chamber structures to prepare liposomes at a larger scale (up to 320 mL/min or 20 L/h) than the commercially available devices. This design demonstrated high productivity and better control of liposome size and polydispersity index (PDI) than conventional liposome preparation methods. The microfluidic swirl mixer devices were used to produce curcumin-loaded liposomes under different processing conditions which were later characterized and studied in vitro to evaluate their efficiency as DDSs. The obtained results demonstrated that the liposomes can effectively deliver curcumin into cancer cells. Therefore, the microfluidic swirl mixers are promising devices for reproducible and scalable manufacturing of DDSs.

Highly selective performance of rationally designed antimicrobial peptides based on ponericin-W1.

Antimicrobial peptides (AMPs) or host-defence peptides act by penetrating and disrupting the bacterial membranes and are therefore less prone to antimicrobial resistance (AMR) compared to conventional antibiotics. However, there are still many challenges in the clinical application of the naturally occurring AMPs which necessitates further studies to establish the relationship between the chemical structure of AMPs and their antimicrobial activity and selectivity. Herein, we report a study on the relationship between the chemical structure and the biological activity of a series of rationally designed AMPs derived from Ponericin-W1, a naturally occurring AMP from ants. The peptides were designed by modification of the hydrophobic and hydrophilic regions of the lead peptide sequence in a systematic way. Their antibacterial and hemolytic activities were determined in vitro. The antibacterial activity of a representative peptide, At5 was also tested in a mouse model of skin wound infection. Furthermore, the relationship between the physicochemical properties of the peptides and their antibacterial activity was investigated. Replacing the cationic amino acids in the hydrophobic region of the peptides with hydrophobic amino acids enhanced their antibacterial activity and increasing the number of cationic amino acids in the hydrophilic region reduced their toxicity to human red blood cells and thus improved their selectivity for bacteria. Four of the designed peptides, coded as At3, At5, At8, and At10, displayed considerable antibacterial activity and high selectivity for bacteria. At5 also accelerated the wound healing in mice indicating high in vivo efficiency of this peptide. The peptides were more effective against Gram-negative bacteria and no AMR was developed against them in the bacteria even after 25 generations. The results from this study can provide a better understanding of the structural features required for strong antibacterial activity and selectivity, and serve as a guide for the future rational design of AMPs.

Anticancer effect of rationally designed α-helical amphiphilic peptides.

Anticancer peptides (ACPs) have attracted increasing attention in cancer therapy due to their unique mechanism of action on cancer cells. The main challenge is to establish the correlation between their physicochemical properties and their selectivity and anticancer effect, leading to a clear design strategy. In this study, a series of new α-helical short peptides (coded At1-At12) with different anticancer activities were systematically designed with different amphiphilicity based on a natural α-helical antimicrobial peptide (AMP) derived from ant. Three of the designed peptides, At7, At10 and At11, showed considerable anticancer activity with low toxicity to normal skin fibroblasts. The high selectivity of the peptides is attributed to their balanced amphiphilicity and cationic nature which favours binding to the outer membrane of negatively charged cancer cells over the neutral membrane of normal mammalian cells. In addition to rapid membrane penetration, the designed peptides also damaged the mitochondria and induced mitochondrial membrane depolarization. Moreover, these peptides were found to induce apoptosis in cancer cells by up-regulating the expression of apoptotic proteins Bax and Caspase-3, down-regulating the apoptotic protein Bcl-2, and activating the Caspase enzyme-linked reaction. The results of this study reveal the potential of these peptides for clinical applications, and provide a guidance for further development of highly selective anticancer medications.

Designed Antitumor Peptide for Targeted siRNA Delivery into Cancer Spheroids.

Antimicrobial/anticancer peptides (AMPs/ACPs) have shown promising results as new therapeutic agents in cancer thearpy. Among them, the designed amphiphilic α-helical peptide G(IIKK)3I-NH2 (G3) displayed great affinity and specificity in targeting cancer cells. Here, we report new insights on how G3 penetrates cancer cells. G3 showed high specificity to HCT-116 colon cancer cells compared to the HDFs (human neonatal primary dermal fibroblasts) control. With high concentrations of peptide, a clear cancer cell membrane disruption was observed through SEM. Gene knockdown of the endocytic pathways demonstrated that an energy-dependent endocytic pathway is required for the uptake of the peptide. In addition, G3 can protect and selectively deliver siRNAs into cancer cells and successfully modulated their gene expression. Gene delivery was also tested in 3D cancer spheroids and showed deep penetration delivery into the cancer spheroids. Finally, the in vivo toxicity of G3 was evaluated on zebrafish embryos, showing an increasing toxicity effect with concentration. However, the toxicity of the peptide was attenuated when complexed with siRNA. In addition, negligible toxicity was observed at the concentration range for efficient gene delivery. The current results demonstrate that G3 is promising as an excellent agent for cancer therapy.

Stiffness-tuneable nanocarriers for controlled delivery of ASC-J9 into colorectal cancer cells.

HYPOTHESIS: One of the main challenges in cancer therapy is the poor water solubility of many anticancer drugs which results in low bioavailability at the tumour sites and reduced efficacy. The currently available polymer-based anticancer drug delivery systems often suffer from low encapsulation efficiency, uncontrolled release, and lack of long-term stability. Herein, we report the development of novel stiffness-tuneable core-shell nanocarriers composed of naturally derived polymers silk fibroin (SF) and sodium alginate (SA) inside a liposomal shell for enhanced cellular uptake and controlled release of hydrophobic anticancer agent ASC-J9 (Dimethylcurcumin). It is anticipated that the stiffness of the nanocarriers has a significant effect on their cellular uptake and anticancer efficacy. EXPERIMENTS: The nanocarriers were prepared by thin film hydration method followed by extrusion and cross-linking of SA to obtain a uniform size and shape, avoiding harsh processing conditions. The structural transformation of SF in the nanocarriers induced by SA crosslinking was determined using Fourier transform infrared (FTIR) spectroscopy. The size, zeta potential, morphology and stiffness of the nanocarriers were measured using dynamic light scattering (DLS), transmission electron microscopy (TEM) and atomic force microscopy (AFM). Drug loading and release were measured using UV-Vis spectrophotometry. The cellular uptake and anticancer efficacy of the nanocarriers were studied in HCT 116 human colorectal adenocarcinoma cells and 3D tumour spheroids using high content microscopy. FINDINGS: The synthesized nanocarriers had high encapsulation efficiency (62-78%) and were physically stable for up to 5 months at 4 ˚C. The release profile of the drug from the nanocarriers was directed by their stiffness and was easily tuneable by changing the ratio of SF to SA in the core. Furthermore, the designed nanocarriers improved the cellular uptake and anticancer activity of ASC-J9, and enhanced its tumour penetration in HCT 116 3D colorectal cancer spheroids. These findings suggest that the designed core-shell nanocarriers can be used as a highly efficient drug delivery system for cancer therapy.

Cell guidance on peptide micropatterned silk fibroin scaffolds.

Guiding neuronal cell growth is desirable for neural tissue engineering but is very challenging. In this work, a self-assembling ultra-short surfactant-like peptide I3K which possesses positively charged lysine head groups, and hydrophobic isoleucine tails, was chosen to investigate its potential for guiding neuronal cell growth. The peptides were able to self-assemble into nanofibrous structures and interact strongly with silk fibroin (SF) scaffolds, providing a niche for neural cell attachment and proliferation. SF is an excellent biomaterial for tissue engineering. However neuronal cells, such as rat PC12 cells, showed poor attachment on pure regenerated SF (RSF) scaffold surfaces. Patterning of I3K peptide nanofibers on RSF surfaces significantly improved cellular attachment, cellular density, as well as morphology of PC12 cells. The live / dead assay confirmed that RSF and I3K have negligible cytotoxicity against PC12 cells. Atomic force microscopy (AFM) was used to image the topography and neurite formation of PC12 cells, where results revealed that self-assembled I3K nanofibers can support the formation of PC12 cell neurites. Immunolabelling also demonstrated that coating of I3K nanofibers onto the RSF surfaces not only increased the percentage of cells bearing neurites but also increased the average maximum neurite length. Therefore, the peptide I3K could be used as an alternative to poly-l-lysine for cell culture and tissue engineering applications. As micro-patterning of neural cells to guide neurite growth is important for developing nerve tissue engineering scaffolds, inkjet printing was used to pattern self-assembled I3K peptide nanofibers on RSF surfaces for directional control of PC12 cell growth. The results demonstrated that inkjet-printed peptide micro-patterns can effectively guide the cell alignment and organization on RSF scaffold surfaces, providing great potential for nerve regeneration applications.

Silk Fibroin as a Functional Biomaterial for Drug and Gene Delivery.

Silk is a natural polymer with unique physicochemical and mechanical properties which makes it a desirable biomaterial for biomedical and pharmaceutical applications. Silk fibroin (SF) has been widely used for preparation of drug delivery systems due to its biocompatibility, controllable degradability and tunable drug release properties. SF-based drug delivery systems can encapsulate and stabilize various small molecule drugs as well as large biological drugs such as proteins and DNA to enhance their shelf lives and control the release to enhance their circulation time in the blood and thus the duration of action. Understanding the properties of SF and the potential ways of manipulating its structure to modify its physicochemical and mechanical properties allows for preparation of modulated drug delivery systems with desirable efficacies. This review will discuss the properties of SF material and summarize the recent advances of SF-based drug and gene delivery systems. Furthermore, conjugation of the SF to other biomolecules or polymers for tissue-specific drug delivery will also be discussed.