Hybrid gum tragacanth/sodium alginate hydrogel reinforced with silver nanotriangles for bacterial biofilm inhibition.

Biomaterial associated bacterial infections are indomitable to treatment due to the rise in antibiotic resistant strains, thereby triggering the need for new antibacterial agents. Herein, composite bactericidal hydrogels were formulated by incorporating silver nanotriangles (AgNTs) inside a hybrid polymer network of Gum Tragacanth/Sodium Alginate (GT/SA) hydrogels. Physico-chemical examination revealed robust mechanical strength, appreciable porosity and desirable in vitro enzymatic biodegradation of composite hydrogels. The antibacterial activity of AgNT-hydrogel was tested against planktonic and biofilm-forming Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria. For all the strains, AgNT-hydrogel showed a dose-dependent decrease in bacterial growth. The addition of AgNT-hydrogels (40-80 mg ml-1) caused 87% inhibition of planktonic biomass and up to 74% reduction in biofilm formation. Overall, this study proposes a promising approach for designing antibacterial composite hydrogels to mitigate various forms of bacterial infection.

Biomaterials-Based Regenerative Strategies for Skin Tissue Wound Healing.

Skin tissue wound healing proceeds through four major stages, including hematoma formation, inflammation, and neo-tissue formation, and culminates with tissue remodeling. These four steps significantly overlap with each other and are aided by various factors such as cells, cytokines (both anti- and pro-inflammatory), and growth factors that aid in the neo-tissue formation. In all these stages, advanced biomaterials provide several functional advantages, such as removing wound exudates, providing cover, transporting oxygen to the wound site, and preventing infection from microbes. In addition, advanced biomaterials serve as vehicles to carry proteins/drug molecules/growth factors and/or antimicrobial agents to the target wound site. In this review, we report recent advancements in biomaterials-based regenerative strategies that augment the skin tissue wound healing process. In conjunction with other medical sciences, designing nanoengineered biomaterials is gaining significant attention for providing numerous functionalities to trigger wound repair. In this regard, we highlight the advent of nanomaterial-based constructs for wound healing, especially those that are being evaluated in clinical settings. Herein, we also emphasize the competence and versatility of the three-dimensional (3D) bioprinting technique for advanced wound management. Finally, we discuss the challenges and clinical perspective of various biomaterial-based wound dressings, along with prospective future directions. With regenerative strategies that utilize a cocktail of cell sources, antimicrobial agents, drugs, and/or growth factors, it is expected that significant patient-specific strategies will be developed in the near future, resulting in complete wound healing with no scar tissue formation.

GNP-CeO2- polyaniline hybrid hydrogel for electrochemical detection of peroxynitrite anion and its integration in a microfluidic platform.

Peroxynitrite anion (ONOO-) is an important in vivo oxidative stress biomarker whose aberrant levels have pathophysiological implications. In this study, an electrochemical sensor for ONOO- detection was developed based on graphene nanoplatelets-cerium oxide nanocomposite (GNP-CeO2) incorporated polyaniline (PANI) conducting hydrogels. The nanocomposite-hydrogel platform exhibited distinct synergistic advantages in terms of large electroactive surface coverage and providing a conductive pathway for electron transfer. Besides, the 3D porous structure of hydrogel integrated the GNP-CeO2 nanocomposite to provide hybrid materials for the evolution of catalytic activity towards electrochemical oxidation of ONOO-. Various microscopic and spectroscopic characterization techniques endorsed the successful formation of GNP-CeO2-PANI hydrogel. Cyclic voltammetry (CV) measurements of GNP-CeO2-PANI hydrogel modified screen-printed electrodes (SPE) were carried out to record the current changes influenced by ONOO-. The prepared sensor demonstrated a significant dose-dependent increase in CV peak current within a linear range of 5-100 µM (at a potential of 1.12 V), and a detection limit of 0.14 with a sensitivity of 29.35 ± 1.4 µA µM-1. Further, a customized microfluidic flow system was integrated with the GNP-CeO2-PANI hydrogel modified SPE to enable continuous electrochemical detection of ONOO- at low sample volumes. The developed microfluidic electrochemical device demonstrated an excellent sensitivity towards ONOO- under optimal experimental conditions. Overall, the fabricated microfluidic device with hybrid hydrogels as electrochemical interfaces provides a reliable assessment of ONOO- levels. This work offers considerable potential for understanding the oxidative stress-related disease mechanisms through determination of ONOO- in biological samples.

Toward Designing of Anti-infective Hydrogels for Orthopedic Implants: From Lab to Clinic.

An alarming increase in implant failure incidence due to microbial colonization on the administered orthopedic implants has become a horrifying threat to replacement surgeries and related health concerns. In essence, microbial adhesion and its subsequent biofilm formation, antibiotic resistance, and the host immune system's deficiency are the main culprits. An advanced class of biomaterials termed anti-infective hydrogel implant coatings are evolving to subdue these complications. On this account, this review provides an insight into the significance of anti-infective hydrogels for preventing orthopedic implant associated infections to improve the bone healing process. We briefly discuss the clinical course of implant failure, with a prime focus on orthopedic implants. We identify the different anti-infective coating strategies and hence several anti-infective agents which could be incorporated in the hydrogel matrix. The fundamental design criteria to be considered while fabricating anti-infective hydrogels for orthopedic implants will be discussed. We highlight the different hydrogel coatings based on the origin of the polymers involved in light of their antimicrobial efficacy. We summarize the relevant patents reported in the prevention of implant infections, including orthopedics. Finally, the challenges concerning the clinical translation of the aforesaid hydrogels are described, and considerable solutions for improved clinical practice and better future prospects are proposed.

Dual-emission copper nanoclusters-based ratiometric fluorescent probe for intracellular detection of hydroxyl and superoxide anion species.

A fluorescent nanoprobe based on copper nanoclusters (CuNCs) has been developed for ratiometric detection of hydroxyl radicals (•OH) and superoxide anion radicals (O2•-). Two differently luminescent CuNCs, namely cyan-emissive poly(methacrylic acid)-protected copper nanoclusters (PCuNCs) and orange-emissive bovine serum albumin-protected CuNCs (BCuNCs), were conjugated to obtain a hybrid, dual-emission nanoprobe (PCuNCs-BCuNCs) with the corresponding peaks at 445 nm and 652 nm at an excitation wavelength of 360 nm. In particular, the fluorescence peak at 445 nm gradually enhanced with the incremental addition of •OH and O2•-. However, the fluorescence emission at 652 nm was greatly quenched in the presence of •OH, while in case of O2•-, the fluorescence intensity remained constant. The differential response of the PCuNCs-BCuNCs towards •OH and O2•- formed the basis of ratiometric detection. Under optimal conditions, the PCuNCs-BCuNCs exhibited good sensitivity and linearity towards •OH and O2•- with limits of detection of 0.15 µM and 1.8 µM, respectively. Moreover, the nanoprobe exhibited high selectivity for •OH and O2•- over other potential ROS interferences. Besides, PCuNCs-BCuNCs were eventually applied for qualitative and quantitative ratiometric assessment of intracellular •OH and O2•- in L-132 cells. Therefore, this strategy unveils a new potential for copper nanocluster-based sensing of ROS.

PMAA-CeO2 nanoparticle-based paper microfluidic device with customized image processing software for antioxidant assay.

Despite recent advancements in the field of microfluidic paper-based analytical devices (µPADs), a key challenge remains in developing a simple and efficient µPAD with customized imaging capabilities for antioxidant assays. In the present study, we report a facile approach for µPAD fabrication through the application of transparent nail paint leading to creation of hydrophobic barriers and well-defined channels. The resultant µPADs were then characterized through scanning electron microscopy and contact angle measurements. The resolution and functional features of the fabricated µPAD were amenable to the intended assay. The µPAD's impregnated poly(methacrylic acid) (PMAA)-coated cerium oxide (CeO2) nanoparticles oxidized the 3,3',5,5'-tetramethylbenzidine (TMB) leading to the formation of a blue-colored charge-transfer complex. The addition of different antioxidant standard solutions resulted in a reduction in the blue color in a dose-dependent manner which could be observed visually. The color intensity of the PMAA-CeO2 nanoparticle@TMB oxidation product was inversely proportional to the antioxidant concentration and was measured using customized in-house MATLAB-based image processing software. Importantly, PMAA-CeO2 nanoparticle-based µPADs demonstrated good analytical characteristics and were able to be stored for long periods without any loss of activity. Moreover, potential interferents did not pose any threat to the colorimetric signal read-out for determination of antioxidant activity. The developed method was further applied for the assessment of antioxidant activity in a variety of tea samples and performed satisfactorily in comparison with a commonly used antioxidant detection method. Collectively, the developed µPAD-based platform holds great potential as a low-cost, convenient, portable and reliable method for pursuing various on-site antioxidant assays. Graphical Abstract.

Near-infrared stimulated hydrogel patch for photothermal therapeutics and thermoresponsive drug delivery.

Nanotechnology driven cancer theranostics hold potential as promising future clinical modalities. Currently, there is a strong emphasis on the development of combinational modalities, especially for cancer treatment. In this study, we present a topical hydrogel patch for nanomaterial-assisted photothermal therapeutics as well as for on-demand drug delivery application. The patch was derived from interpenetrating networks (IPNs) of alginate (Alg) and polyacrylamide (PAAm) in weight ratio 8:1 by free radical polymerization. The patch interiors were composed of hybrid nanostructures derived from gold nanorods (AuNRs) anchored onto polyvinylpyrrolidone (PVP) functionalized graphene oxide (PVP-nGO) to form PVP-nGO@AuNRs hybrids. Field emission scanning electron microscopy (FE-SEM) images revealed the porous nature of the hybrid hydrogel patch with an average pore size of ~28.60 ± 3.10 µm. Besides, functional characteristics of the hybrid patch, such as mechanical strength, viscoelastic and swelling behavior, were investigated. Under near-infrared (NIR) radiation exposure, the hybrid patch exhibited photothermal properties such as surface temperature rise to 75.16 ± 0.32 °C, sufficient to ablate cancer cells thermally. Besides, the heat generated in the hybrid patch could be transmitted to an underlying hydrogel (mimicking skin tissue) when stacked together without much loss. Under cyclic photothermal heating, the patch could retain its photothermal stability for four cycles. Furthermore, the hybrid patch demonstrated NIR stimulated drug release, which was evaluated using methotrexate (MTX, water-insoluble anticancer drug) and rhodamine B (RhB, water-soluble dye). Taken together, this work provides a new dimension towards the development of externally placed hydrogel patches for thermal destruction of localized solid tumors and tunable delivery of chemotherapeutic drugs at the target site.

Progress in 3D bioprinting technology for tissue/organ regenerative engineering.

Escalating cases of organ shortage and donor scarcity worldwide are alarming reminders of the need for alternatives to allograft tissues. Within the last three decades, research efforts in the field of regenerative medicine and tissue engineering continue to address the unmet need for artificial tissues and organs for transplant. Work in the field has evolved to create what we consider a new field, Regenerative Engineering, defined as the Convergence of advanced materials science, stem cell science, physics, developmental biology and clinical translation towards the regeneration of complex tissues and organ systems. Included in the regenerative engineering paradigm is advanced manufacturing. Three-dimensional (3D) bioprinting is a promising and innovative biofabrication strategy to precisely position biologics, including living cells and extracellular matrix (ECM) components, in the prescribed 3D hierarchal organization to create artificial multi-cellular tissues/organs. In this review, we outline recent progress in several bioprinting technologies used to engineer scaffolds with requisite mechanical, structural, and biological complexity. We examine the process parameters affecting bioprinting and bioink-biomaterials and review notable studies on bioprinted skin, cardiac, bone, cartilage, liver, lung, neural, and pancreatic tissue. We also focus on other 3D bioprinting application areas including cancer research, drug testing, high-throughput screening (HTS), and organ-on-a-chip models. We also highlight the current challenges associated with the clinical translation of 3D bioprinting and conclude with the future perspective of bioprinting technology.

Polydopamine functionalized hydrogel beads as magnetically separable antibacterial materials.

In the present study, magnetically separable hydrogel beads of ionically cross-linked alginate were functionalized with polydopamine (PDA). The rationale behind this was to enhance the structural stability and antibacterial profile of PDA/Alg/Fe3O4 beads (K3). Incorporation of superparamagnetic magnetite (Fe3O4) nanoparticles endowed the hydrogel beads with magnetism. X-ray diffraction (XRD) analysis revealed the successful formation of pure Alg/Fe3O4 nanoparticles having an inverse spinel structure. Vibrating sample magnetometry (VSM) confirmed their superparamagnetic behaviour with M s values of 36.18 and 30.46 emu g-1 at 5 and 300 K, respectively. High resolution-transmission electron microscopy (HR-TEM) images showed alginate capping and the size of the Alg/Fe3O4 nanoparticles (∼8 nm). The successful deposition of PDA granules on the K3 bead surface was verified by field emission-scanning electron microscopy (FE-SEM). The PDA functionalization was further justified by VSM, XRD and Fourier-transform infrared spectroscopy (FT-IR). During swelling experiments, K3 beads displayed appreciable structural stability compared to bare/non-functionalized beads. Wettability studies revealed K3 beads to be hydrophilic with a contact angle of ∼55°. Rheological parameters including storage modulus (G') and shear viscosity of K3 increased upon PDA functionalization. During antibacterial tests, K3 strongly inhibited E. coli, S. typhi, S. aureus and L. monocytogenes in a concentration and time dependent manner. Fluorescence staining experiments showed that K3 could greatly alter the bacterial membrane integrity. Reusability experiments with K3 beads substantiated their effective broad-spectrum antibacterial performance for three consecutive cycles.

Carbon dots incorporated polymeric hydrogels as multifunctional platform for imaging and induction of apoptosis in lung cancer cells.

Multifunctional hydrogels offer a seemingly efficient system for delivery of drugs and bioimaging modalities. The present study deals with the facile development of chitosan-based hydrogel formulation composed of highly fluorescent carbon dots (CDs) and loaded with a model anticancer drug, 5-Fluorouracil (5-FU). Herein, CDs were embedded firmly within the hydrogel matrices (CD-HY) via non-covalent interactions during the ionic cross-linking reaction. Furthermore, these hydrogels could effectively encapsulate 5-FU through hydrophobic interactions to form 5-FU@CD-HY. In this way, it was possible to combine the merits of both CDs and 5-FU on a common platform for monitoring the cellular uptake as well as therapeutic effects. Field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) illustrated the porous nature and formation of 5-FU@CD-HY. Besides, functional characteristics of 5-FU@CD-HY such as surface area, mechanical strength, swelling behavior and drug release were investigated. In vitro studies revealed the multifunctional aspects of 5-FU@CD-HY in monitoring the cellular uptake and inflicting apoptosis in A549 cells. Green fluorescence of CDs in 5-FU@CD-HY aided the qualitative and quantitative assessment of cellular uptake. In addition to this, the fluorescence of CDs could be used to detect apoptosis instigated by 5-FU, eliminating the need for multiplex dyes. Induction of apoptosis in 5-FU@CD-HY treated cells was evidenced by changes in cell cycle distributions and visualization of characteristic apoptotic bodies through FE-SEM. Apoptotic gene expression studies further elucidate the molecular mechanism involved in eliciting apoptosis. Thus, hydrogels mediated integration of fluorescent CDs with chemotherapeutic agents provides a new dimension for the potential use of hydrogels in cancer theranostics.

Chemically Cross-Linked Hybrid Nanogels of Alginate and PAMAM Dendrimers as Efficient Anticancer Drug Delivery Vehicles.

Proper choice and design of nanocarriers is imperative to achieve the desired therapeutic benefits. Herein, we report a facile methodology for preparation of chemically cross-linked AG-G5 hybrid nanogels of alginate (AG) and G5.0 poly(amidoamine) (PAMAM) dendrimer via carbodiimide chemistry. The rationale behind the formulation of AG-G5 nanogels is to attain effective and sustained delivery of chemotherapeutic agents. Physical entrapment of anticancer drug epirubicin (EPI) within AG-G5 nanogels endows them with therapeutic properties. Analytical techniques such as zeta potential (ζ) measurements, field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), and Fourier transform infrared spectroscopy (FTIR) confirm the integration of PAMAM dendrimer with alginate structure. Thermal, swelling studies, and surface area estimations suggest improved stability and porosity of AG-G5 nanogels. Moreover, AG-G5 nanogels exhibited significantly better mechanical properties and pH dependent release of EPI than AG nanogels. Fluorescence microscopy, cell viability assay, cell cycle analysis and FE-SEM imaging indicated apoptosis inducing potential of EPI⊂AG-G5 nanogels by enhanced intracellular EPI accumulation in breast cancer (MCF-7) cells. Overall, our results put forth AG-G5 hybrid nanogels as prospective candidates to achieve enhanced anticancer effects in vitro.

Multicomponent 5-fluorouracil loaded PAMAM stabilized-silver nanocomposites synergistically induce apoptosis in human cancer cells.

Herein, we report the development of a poly(amidoamine) (PAMAM) dendrimer based multicomponent therapeutic agent for in vitro cancer therapy applications. In this approach, Generation 5 (G5) PAMAM dendrimers stabilizing silver nanoparticle surface (DsAgNPs) were used to encapsulate anticancer drug 5-fluorouracil (5-FU) to attain synergism in cancer cells. 5-FU loaded DsAg nanocomposites (5-FU@DsAgNCs) were characterized by UV-visible spectroscopy, transmission electron microscopy, X-ray diffraction, and nuclear magnetic resonance measurements. In vitro release studies certify the sustained release of 5-FU from nanocomposites. 5-FU@DsAgNCs were found to elicit a synergistic antiproliferative effect in A549 (human lung cancer) and MCF-7 (human breast cancer) cells with IC50 of 5 µg mL(-1) and 1.5 µg mL(-1), and combination index (CI) values of 0.242 and 0.178, respectively. Atomic absorption spectroscopic analyses indicated higher cellular uptake of Ag in MCF-7 than that in A549 cancer cells. Nuclear and morphological alterations, typical of apoptosis induction, were revealed by fluorescence and scanning electron microscopy imaging. An increment in reactive oxygen species (ROS) levels was measured; this indicated the induction of oxidative stress in both 5-FU@DsAgNC treated cell types. Taken together, the apoptotic effects of 5-FU@DsAgNC were more prominent in MCF-7 than in A549 cancer cells. Finally, gene expression studies suggested triggering of the p53 mediated caspase signalling gene cascade in 5-FU@DsAgNC treated cells. The strategy to use dendrimer technology to design multicomponent 5-FU@DsAgNCs is quite promising for simultaneous delivery of 5-FU and DsAgNPs to achieve synergistic anticancer effects.

Self-Assembled Hybrids of Fluorescent Carbon Dots and PAMAM Dendrimers for Epirubicin Delivery and Intracellular Imaging.

Advanced nanomaterials integrating imaging and therapeutic modalities on a single platform offers a new horizon in current cancer treatment strategies. Recently, carbon dots (CQDs) have been successfully employed for bioimaging of cancer cells. In the present study, luminescent CQDs with anionic terminus and cationic acetylated G5 poly(amido amine) (G5-Ac85) dendrimers were combined via noncovalent interactions to form self-assembled fluorescent hybrids. The fluorescence of CQDs in hybrids is enhanced in the vicinity of primary amine groups of dendrimers, making them suitable as cellular imaging probes. Encapsulation of chemo-drug epirubicin (EPI) in the dendrimer interiors endowed the fluorescent hybrids with therapeutic potential. The in vitro release of an entrapped EPI drug from CQDs@EPI⊂G5-Ac85 hybrids was faster in an acidic environment than under physiological conditions. Herein, multifunctional CQDs@EPI⊂G5-Ac85 hybrids serve as a dual-emission delivery system, to track the intracellular distribution and cytotoxic effects of EPI drugs. Green emission properties of CQDs were used for fluorescence microscopic imaging and cellular uptake by flow cytometry. Cell cycle analysis, field-emission scanning electron microscopy (FE-SEM), reactive oxygen species (ROS) generation, and up-regulation of apoptotic signaling genes unanimously demonstrated the apoptosis inducing ability of CQDs@EPI⊂G5-Ac85 hybrids in breast cancer (MCF-7) cells. Therefore, we have evaluated CQDs@EPI⊂G5-Ac85 hybrids as prospective candidates to achieve simultaneous imaging and drug delivery in cancer cells.

Perturbation of cellular mechanistic system by silver nanoparticle toxicity: Cytotoxic, genotoxic and epigenetic potentials.

Currently the applications of silver nanoparticles (Ag NPs) are gaining overwhelming response due to the advancement of nanotechnology. However, only limited information is available with regard to their toxicity mechanism in different species. It is very essential to understand the complete molecular mechanism to explore the functional and long term applications of Ag NPs. Ag NPs could be toxic at cellular, subcellular, biomolecular, and epigenetic levels. Toxicity effects induced by Ag NPs have been evaluated using numerous in vitro and in vivo models, but still there are contradictions in interpretations due to disparity in methodology, test endpoints and several other model parameters which needs to be considered. Thus, this review article focuses on the progressive elucidation of molecular mechanism of toxicity induced by Ag NPs in various in vitro and in vivo models. Apart from these, this review also highlights the various ignored factors which are to be considered during toxicity studies.

Dual-functional carbon dots-silver@zinc oxide nanocomposite: in vitro evaluation of cellular uptake and induction of apoptosis.

Carbon dots (CDs) are novel bioimaging tools with fascinating fluorescence properties. We report here the development of novel CDs decorated on a silver-zinc oxide (CD-Ag@ZnO) nanocomposite (NC) consisting of highly fluorescent CDs and Ag@ZnO. The CD-Ag@ZnO NC was characterized by various analytical techniques. Our work provides an insight into the application of this CD-Ag@ZnO NC in monitoring cellular uptake and mediating apoptotic effects in MCF-7 and A549 cancer cell lines. By monitoring the simultaneous green fluorescence emission of the CDs, the distribution of the CD-Ag@ZnO NC could be followed, eliminating the need to use fluorescent organic dyes. Fluorescence microscopy and atomic absorption spectrometry were used for the qualitative and quantitative assessment of cellular uptake. In vitro studies of cancer cells treated with CD-Ag@ZnO NC revealed concentration-dependent cytotoxic effects via the induction of apoptosis. Fluorescence and scanning electron microscopy were used to study the characteristic nuclear and morphological changes during apoptosis. We used flow cytometry to quantify the reactive oxygen species and the reverse transcriptase polymerase chain reaction to study apoptotic gene expression. The role of reactive oxygen species in eliciting the apoptotic gene cascade was also studied. Intriguingly, the multifunctional CD-Ag@ZnO NC has a tendency to evoke apoptosis while allowing real-time intracellular trafficking, which may be of huge relevance in cancer theranostic applications.

Antibacterial activity and mechanism of Ag-ZnO nanocomposite on S. aureus and GFP-expressing antibiotic resistant E. coli.

Emergence of multi-resistant organisms (MROs) leads to ineffective treatment with the currently available medications which pose a great threat to public health and food technology sectors. In this regard, there is an urgent need to strengthen the present therapies or to look over for other potential alternatives like use of "metal nanocomposites". Thus, the present study focuses on synthesis of silver-zinc oxide (Ag-ZnO) nanocomposites which will have a broad-spectrum antibacterial activity against Gram-positive and Gram-negative bacteria. Ag-ZnO nanocomposites of varied molar ratios were synthesized by simple microwave assisted reactions in the absence of surfactants. The crystalline behavior, composition and morphological analysis of the prepared powders were evaluated by X-ray diffraction, infrared spectroscopy, field emission scanning electron microscopy (FE-SEM) and atomic absorption spectrophotometry (AAS). Particle size measurements were carried out by transmission electron microscopy (TEM). Staphylococcus aureus and recombinant green fluorescent protein (GFP) expressing antibiotic resistant Escherichia coli were selected as Gram-positive and Gram-negative model systems respectively and the bactericidal activity of Ag-ZnO nanocomposite was studied. The minimum inhibitory concentration (MIC) and minimum killing concentration (MKC) of the nanocomposite against the model systems were determined by visual turbidity analysis and optical density analysis. Qualitative and quantitative assessments of its antibacterial effects were performed by fluorescent microscopy, fluorescent spectroscopy and Gram staining measurements. Changes in cellular morphology were examined by atomic force microscopy (AFM), FE-SEM and TEM. Finally, on the basis of the present investigation and previously published reports, a plausible antibacterial mechanism of Ag-ZnO nanocomposites was proposed.

Ferritin nanocages: a novel platform for biomedical applications.

Ferritin is a ubiquitous iron storage protein responsible for maintaining the iron homeostasis in living organism and thereby protects the cell from oxidative damage. The ferritin protein cages have been used as a reaction vessel for the synthesis of various non-native metallic nanoparticles inside its core and also used as a nanocarrier for various applications. Lack of suitable non-viral carrier for targeted delivery of anticancer drugs and imaging agents is the major problem in cancer therapy and diagnosis. The pH dependent reversible assembling and disassembling property of ferritin renders it as a suitable candidate for encapsulating a variety of anticancer drugs and imaging probes. Ferritins external surface is chemically and genetically modifiable which can serve as attachment site for tumor specific targeting peptides or moieties. Recent studies, further establishes ferritin as a multifunctional nanocarrier for targeted cancer diagnosis and therapy. Moreover, the biological origin of these protein cages makes it a biocompatible nanocarrier that stabilizes and protects the enclosed particles from the external environment without provoking any toxic or immunogenic responses. This review mainly focuses on the application of ferritin nanocages as a novel non-viral nanocarrier for cancer therapy and it also highlights various biomedical applications of ferritin nanocages.