DNA and Nanomaterials: A Functional Combination for DNA Sensing.

Recent decades have experienced tough situations due to the lack of reliable diagnostic facilities. The most recent cases occurred during the pandemic, where researchers observed the lack of diagnostic facilities with precision. Microorganisms and viral disease's ability to escape diagnosis has been a global challenge. DNA always has been a unique moiety with a strong and precise base-paired structure. DNA in human and foreign particles makes identification possible through base pairing. Since then, researchers have focused heavily on designing diagnostic assays targeting DNA in particular. Moreover, DNA nanotechnology has contributed vastly to designing composite nanomaterials by combining DNA/nucleic acids with functional nanomaterials and inorganic nanoparticles exploiting their physicochemical properties. These nanomaterials often exhibit unique or enhanced properties due to the synergistic activity of the many components. The capabilities of DNA and additional nanomaterials have shown the combination of robust and advanced tailoring of biosensors. Preceding findings state that the conventional strategies have exhibited certain limitations such as a low range of target detection, less biodegradability, subordinate half-life, and high susceptibility to microenvironments; however, a DNA-nanomaterial-based biosensor has overcome these limitations meaningfully. Additionally, the unique properties of nucleic acids have been studied extensively due to their high signal conduction abilities. Here, we review recent studies on DNA-nanomaterial-based biosensors, their mechanism of action, and improved/updated strategies in vivo and in situ. Furthermore, this review highlights the recent methodologies on DNA utilization to exploit the interfacial properties of nanomaterials in DNA sensing. Lastly, the review concludes with the limitations/challenges and future directions.

Hydrogel-Based Biosensors for Effective Therapeutics.

Nanotechnology and polymer engineering are navigating toward new developments to control and overcome complex problems. In the last few decades, polymer engineering has received researchers' attention and similarly, polymeric network-engineered structures have been vastly studied. Prior to therapeutic application, early and rapid detection analyses are critical. Therefore, developing hydrogel-based sensors to manage the acute expression of diseases and malignancies to devise therapeutic approaches demands advanced nanoengineering. However, nano-therapeutics have emerged as an alternative approach to tackling strenuous diseases. Similarly, sensing applications for multiple kinds of analytes in water-based environments and other media are gaining wide interest. It has also been observed that these functional roles can be used as alternative approaches to the detection of a wide range of biomolecules and pathogenic proteins. Moreover, hydrogels have emerged as a three-dimensional (3D) polymeric network that consists of hydrophilic natural or synthetic polymers with multidimensional dynamics. The resemblance of hydrogels to tissue structure makes them more unique to study inquisitively. Preceding studies have shown a vast spectrum of synthetic and natural polymer applications in the field of biotechnology and molecular diagnostics. This review explores recent studies on synthetic and natural polymers engineered hydrogel-based biosensors and their applications in multipurpose diagnostics and therapeutics. We review the latest studies on hydrogel-engineered biosensors, exclusively DNA-based and DNA hydrogel-fabricated biosensors.

Phototherapy: A Conventional Approach to Overcome the Barriers in Oncology Therapeutics.

Cancer disease has outgrown a life-threatening disease. Having reference to preceding reports provided by the International Agency for Research on Cancer, an estimated 9.6 million deaths transpired from cancer worldwide in 2018. Similarly, about 18.1 million new cases of cancer are being reported. The rise in conventional treatments akin to surgeries, chemotherapies, and radiotherapies was enormously observed to eradicate cancer tumors. These studies have shown unfavorable side effects in clinical treatments. Drug resistivity and drug cytotoxicities are also major issues to overcome. Considering these, researchers are developing alternative methods that are robust, economical, and safe. The use of light for therapeutic purposes shows a great history in vitiligo treatment. The combination of an effective activating agent and phototherapy could result as the best alternative with a great outcome to minimize adverse effects on healthy tissues. The utilization of light in the deletion of tumors using photothermal agents, and photosensitizers, hence the phototherapies in oncology were discovered and rapidly involved in the advancement of clinical approach. Here, in this article, we tried to highlight the recent trends in phototherapy and reviewed different types of phototherapy methods in cancer treatments and their latest clinical, preclinical, and in vivo studies.

DNA Hydrogel-Based Nanocomplexes with Cancer-Targeted Delivery and Light-Triggered Peptide Drug Release for Cancer-Specific Therapeutics.

Cancer therapies based on chemotherapeutic drug delive ries have been the most facilitated studies. Recently, peptide drugs have emerged as anticancer drugs due to their less immunogenicity and lower production costs compared with other synthetics. However, still, the side effects of these chemotherapeutics on healthy tissues have been a great concern to deal with, and these side effects are usually caused by off-targeted delivery and unwanted leakage. In addition, peptides are easily degraded by enzyme attacks during delivery. To address these concerns, here, we developed a robust, cancer-specific peptide drug delivery system with negligible cytotoxicity in in vitro. A peptide drug delivery vehicle (Dgel-PD-AuNP-YNGRT) was constructed by stepwise functionalization on a nanoscale DNA hydrogel (Dgel). A cell-penetrating anticancer peptide drug, Buforin IIb, was loaded within the Dgel network via electrostatic attraction followed by AuNP assembly. The AuNPs were employed as photothermal reagents for light-triggered peptide drug release. An additional peptide, including a cancer-targeting YNGRT sequence, was also bound on the Dgel for cancer-cell-targeted delivery. According to the results obtained from the studies employing cancer cells as well as normal cells, Dgel-PD-AuNP-YNGRT nanocomplexes could be delivered specifically to cancer cells, activated by light illumination, and release anticancer peptide drugs to kill cancer cells with no cytotoxicity and negligible hazardous effect on normal cell lines. The obtained cell viability assay suggests that at a high intensity (15 W/cm2), photothermally triggered released peptide drug has shown up to 44% higher kill than only peptide drug treatments in cancer cells. Similarly, the Bradford assay demonstrated that up to 90% of peptide drugs were released with our engineered Dgel-PD-AuNP-YNGRT nanocomplex. The Dgel-PD-AuNP-YNGRT nanocomplex may serve as an ideal anticancer peptide drug delivery platform for safe, cancer-specific targeting and efficient peptide drug delivery in cancer therapy.

Nanohydrogels: Advanced Polymeric Nanomaterials in the Era of Nanotechnology for Robust Functionalization and Cumulative Applications.

In the era of nanotechnology, the synthesis of nanomaterials for advanced applications has grown enormously. Effective therapeutics and functionalization of effective drugs using nano-vehicles are considered highly productive and selectively necessary. Polymeric nanomaterials have shown their impact and influential role in this process. Polymeric nanomaterials in molecular science are well facilitated due to their low cytotoxic behavior, robust functionalization, and practical approach towards in vitro and in vivo therapeutics. This review highlights a brief discussion on recent techniques used in nanohydrogel designs, biomedical applications, and the applied role of nanohydrogels in the construction of advanced therapeutics. We reviewed recent studies on nanohydrogels for their wide applications in building strategies for advantageously controlled biological applications. The classification of polymers is based on their sources of origin. Nanohydrogel studies are based on their polymeric types and their endorsed utilization for reported applications. Nanotechnology has developed significantly in the past decades. The novel and active role of nano biomaterials with amplified aspects are consistently being studied to minimize the deleterious practices and side effects. Here, we put forth challenges and discuss the outlook regarding the role of nanohydrogels, with future perspectives on delivering constructive strategies and overcoming the critical objectives in nanotherapeutic systems.

Tuning Plasmonic Properties of Gold Nanoparticles by Employing Nanoscale DNA Hydrogel Scaffolds.

Noble metals have always fascinated researchers due to their feasible and facile approach to plasmonics. Especially the extensive utilization of gold (Au) has been found in biomedical engineering, microelectronics, and catalysis. Surface plasmonic resonance (SPR) sensors are achievable by employing plasmonic nanoparticles. The past decades have seen colossal advancement in noble metal nanoparticle research. Surface plasmonic biosensors are advanced in terms of sensing accuracy and detection limit. Likewise, gold nanoparticles (AuNPs) have been widely used to develop distinct biosensors for molecular diagnosis. DNA nanotechnology facilitates advanced nanostructure having unique properties that contribute vastly to clinical therapeutics. The critical element for absolute control of materials at the nanoscale is the engineering of optical and plasmonic characteristics of the polymeric and metallic nanostructure. Correspondingly, AuNP's vivid intense color expressions are dependent on their size, shape, and compositions, which implies their strong influence on tuning the plasmonic properties. These plasmonic properties of AuNPs have vastly exerted the biosensing and molecular diagnosis applications without any hazardous effects. Here, we have designed nanoscale X-DNA-based Dgel scaffolds utilized for tuning the plasmonic properties of AuNPs. The DNA nanohydrogel (Dgel) scaffolds engineered with three different X-DNAs of distinct numbers of base pairs were applied. We have designed X-DNA base pair-controlled size-varied Dgel scaffolds and molar ratio-based nano assemblies to tune the plasmonic properties of AuNPs. The nanoscale DNA hydrogel's negatively charged scaffold facilitates quaternary ammonium ligand-modified positively charged AuNPs to flocculate around due to electrostatic charge attractions. Overall, our study demonstrates that by altering the DNA hydrogel scaffolds and the physical properties of the nanoscale hydrogel matrix, the SPR properties can be modulated. This approach could potentially benefit in monitoring diverse therapeutic biomolecules.

Cancer Cell-Specific Enhanced Raman Imaging and Photothermal Therapeutic Effect Based on Reversibly pH-Responsive Gold Nanoparticles.

Stimuli-responsive nanoparticles are favorable for improving the selective delivery and rational vocation that easily avoids the undesirable barriers or side effects, leading to a further improved therapeutic efficiency. Furthermore, multifunctional nanomaterials have been extensively developed as attractive candidates for theranostic reagents for cancer treatment. In this article, we developed reversibly pH-responsive gold nanoparticles (AuNPs) with an enhanced Raman scattering signal as well as an efficient photothermal effect and demonstrated their applications as a theranostic reagent for cancer treatment. Surfaces of these AuNPs were modified with mixed layers of Cy3-modified single-stranded DNA (ssDNA-Cy3) for Raman probing and a negative charge supply and cytochrome C (Cyt C) for pH-responsive charge inversion. This combination of pH-responsive ligands and Raman probes played an important role in inducing the assembly or disassembly of AuNPs corresponding to the neighboring pH, accompanied by an additional highly distinguished Raman signal intensity. An operative reversible response of the AuNPs to pH is endowed with the characteristic behavior of AuNPs with the cancerous cell's acidic microenvironment of low pH. The responsive aggregation of AuNPs in a lower pH medium provides highly amplified signals attributed to well-formed hot spots between the particle surfaces that deliver better Raman scattering signals. The acidic pH-responsive aggregation of the particles also provided efficient photothermal treatments using a long-wavelength laser light with the benefit of deeper penetration for cancer cells. In vitro experiments employing cancer cells and control normal cells well-demonstrated the specificity of the particles to cancer cells in terms of highly enhanced Raman imaging and therapeutic efficiency.