The major limitations
of traditional methods of anticancer drug delivery include systemic
distribution and frequent administration intravenously. To address
these issues, in our present approach, we have fabricated a nano hybrid
silk hydrogel system for localized, targeted, and on-demand delivery
of anticancer drugs. The hybrid system contains a blend of two varieties
of silk protein and doxorubicin (DOX)-loaded folic acid functionalized
single-walled carbon nanotubes (SWCNT-FA/DOX). Owing to the single-walled
carbon nanotube (SWCNT) incorporation, the mechanical strength of
the hybrid silk hydrogel composite enhanced significantly. A slow
and sustained DOX release was recorded over a 14 day study. The amount
of DOX released was determined by concentration of the SWCNT-FA/DOX
payload, rate of silk degradation, pH of the released medium, and
incubation temperature. The intermittent exposure of near-infrared
light to the hybrid gel system stimulated on-demand DOX release. The in vitro studies demonstrated the active targeting of SWCNT-FA/DOX
to folic acid receptor-positive (FR+ve) cancer cells. The
silk hydrogel, being viscoelastic in nature, is easily injectable
to the targeted site. Hence, the developed silk hybrid gel system
may allow its near or intratumoral implantation, where it may act
as a depot for anticancer drug-loaded nanoparticles. The sustained,
targeted, and external-stimuli-dependent DOX released at the localized
tumor site is expected to reduce its systemic side effects and show
an efficient way to treat the cancer.
Silk,
a natural biopolymer, has been used clinically as suture
material over thousands of years and has received much impetus for
a plethora of biomedical applications in the last two decades. Silk
protein isolated from both mulberry and nonmulberry silkworm varieties
gained recognition as a potential biomaterial owing to its affordability
and remarkable physicochemical properties. Molecular studies on the
amino acid composition and conformation of silk proteins interpreted
in the present review provide a critical understanding of the difference
in crystallinity, hydrophobicity, and tensile strength among silkworm
silk proteins. Meticulous silk fibroin (SF) isolation procedures and
innovative processing techniques to fabricate gamut of two-dimensional
(2D) and three-dimensional (3D) matrices including the latest 3D printed
scaffolds have led SF for diverse biomedical applications. Crucial
factors for clinical success of any biomaterial, including biocompatibility,
immune response, and biodegradability, are discussed with particular
emphasis on the lesser-known endemic nonmulberry silk varieties, which
in recent years have gained considerable attention. The tunable biodegradation
and bioresorbable attributes of SF enabled its use in drug delivery
systems, thus proving it as an efficient and specific vehicle for
controlled drug release and targeted drug delivery. Advancements in
fabrication methodologies inspired biomedical researchers to develop
SF-based in vitro tissue models mimicking the spatiotemporal
arrangement and cellular distribution of native tissue. In
vitro tissue models own a unique demand for studying tissue
biology, cellular crosstalks, disease modeling, drug designing, and
high throughput drug screening applications. Significant progress
in silk biomaterial research has evolved into several silk-based healthcare
products in the market. Insights of silk-based products assessed in
the human clinical trials are presented in this review. Overall, the
current review explores the paradigm of the silk structure–function
relationship driving silk-based biomaterials toward tissue engineering,
drug delivery systems, and in vitro tissue models.
The syntheses, characterizations, and biological activities of three organoplatinum compounds, each containing a triazole ring, are discussed. These organometallic compounds demonstrate superior cytotoxicity against osteosarcoma and human breast cancer cells relative to cisplatin, a well-known chemotherapeutic agent used for chemotherapy.
Conventional
systemic chemotherapeutic regimens suffer from challenges
such as nonspecificity, shorter half-life, clearance of drugs, and
dose-limiting toxicity. Localized delivery of chemotherapeutic drugs
through noninvasive spatiotemporally controllable stimuli-responsive
drug delivery systems could overcome these drawbacks while utilizing
drugs approved for cancer treatment. In this regard, we developed
photoelectro active nanocomposite silk-based drug delivery systems
(DDS) exhibiting on-demand drug release in vivo. A functionally modified
single-walled carbon nanotube loaded with doxorubicin (DOX) was embedded
within a cross-linker free silk hydrogel. The resultant nanocomposite
silk hydrogel showed electrical field responsiveness and near-infrared
(NIR) laser-induced hyperthermal effect. The remote application of
these stimuli in tandem or independent manner led to the increased
thermal and electrical conductivity of nanocomposite hydrogel, which
effectively triggered the intermittent on-demand drug release. In
a proof-of-concept in vivo tumor regression study, the nanocomposite
hydrogel was administered in a minimally invasive way at the periphery
of the tumor by covering most of it. During the 21-day study, drastic
tumor regression was recorded upon regular stimulation of nanocomposite
hydrogel with simultaneous or individual external application of an
electric field and NIR laser. Tumor cell death marker expression analysis
uncovered the induction of apoptosis in tumor cells leading to its
shrinkage. Heart ultrasound and histology revealed no cardiotoxicity
associated with localized DOX treatment. To our knowledge, this is
also the first report to show the simultaneous application of electric
field and NIR laser in vivo for localized tumor therapy, and our results
suggested that such strategy might have high clinical translational
potential.
Two new irregular hexagons (6 and 7) were synthesized from a pyrazine motif containing an organometallic acceptor clip [bearing platinum(II) centers] and different neutral donor ligands (4,4'-bipyridine or pyrazine) using a coordination-driven self-assembly protocol. The two-dimensional supramolecules were characterized by multinuclear NMR, mass spectrometry, and elemental analyses. Additionally, one of the macrocycles (6) was characterized by single-crystal X-ray analyses. Macrocycles are unique examples of [2 + 2] self-assembled ensembles that are hexagonal but irregular in shape. These hexagon frameworks require the assembly of only four tectons/subunits. The cytotoxicity of platinum(II)-based macrocycles was studied using various cell lines such as A549 (human lung carcinoma), KB (human oral cancer), MCF7 (human breast cancer), and HaCaT (human skin keratinocyte) cell lines, and the results were compared with those of cisplatin. The smaller macrocycle (7) exhibited a higher cytotoxic effect against all cell types, and its sensitivity was found to be comparable with that of cisplatin for A549 and MCF7 cells. Cell cycle analysis and live propidium iodide staining suggest that the macrocycles 6 and 7 induced a loss of membrane integrity that ultimately might lead to necrotic cell death.
Designing programmable biomaterials that could act as extracellular matrix and permits functionalization is a current need for tissue engineering advancement. DNA based hydrogels are getting significant attention owing to their...
DNA-based nanotechnology has evolved into an autonomous, highly innovative, and dynamic field of research at the nexus of supramolecular chemistry, nanotechnology, materials science, and biotechnology. DNA-based materials, including origami nanodevices,...
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