Drug Delivery Performance Research Articles

Potential application of XC3 (X = B, N) nanosheets in drug delivery of hydroxyurea anticancer drug: a comparative DFT study

The assessment of drug delivery performance of fabricated pristine XC3 monolayers (X = B, N) for the hydroxyurea anticancer drug was performed using periodic DFT calculations. The most stable direction for the adsorption of hydroxyurea drug over the XC3 monolayers was considered and adsorption energies were computed. The adsorption of hydroxyurea on the XC3 monolayers highly depends on the elemental group of X. The BC3 monolayer has stronger adsorption of hydroxyurea drug than the NC3 monolayer. Since pH around malignancy cells is lower than normal cells, we researched drug release around the cancerous cells upon protonation. The solvent energy and adsorption energies obtained for the BC3 monolayer in an aqueous solution are more vital than the NC3 monolayer. The capability of an XC3 monolayer as a vehicle for hydroxyurea drug to treat malignant growth affirmed.

One‐pot synthesis of ICG&Cur@ZIF‐8 nanocomposites with pH‐controlled drug delivery and good photothermal performance

AbstractCombination therapy has shown great potential for effective cancer treatment. In this work, anticancer drug curcumin (Cur) and photothermal agent indocyanine green (ICG) have been encapsulated into the pH‐responsive ZIF‐8 simultaneously to obtain ICG&Cur@ZIF‐8 through one‐pot synthesis method. The drug loading capacity was estimated as 9.6 and 12.3 wt% for Cur and ICG, respectively. As expected, ICG&Cur@ZIF‐8 exhibited the pH‐responsive ICG and Cur delivery, which was ascribed to the decomposition of ZIF‐8 in acidic environment. Moreover, ICG&Cur@ZIF‐8 also showed the high photothermal performance due to the efficient encapsulation of ICG. The co‐delivery of two therapeutic agents may bring more opportunities for biomedical application.

Gold nanorod@void@polypyrrole yolk@shell nanostructures: Synchronous regulation of photothermal and drug delivery performance for synergistic cancer therapy

Synergistic therapy has been emerging as new trend for effective tumor treatment due to synchronous function and cooperative reinforcement of multi therapeutic modalities. Herein, gold nanorods (GNRs) encapsulated into polypyrrole (PPy) shell with tunable void space (GNRs@Void@PPy) showing yolk@shell nanostructures were innovatively designed. The exploitation of dual near-infrared (NIR) absorptive species offered synergistic enhancement of photothermal performance. In addition, the manipulation of the void space between them provided additional benefits of high drug encapsulation efficiency (92.6%) and, interestingly, tumor microenvironment and NIR irradiation triggered targeted drug releasing. Moreover, the GNRs@Void@PPy exhibited excellent biocompatibility, and optimal curative effect by chemo-photothermal synergistic therapy was achieved through both in vitro and in vivo antitumor activity investigation.

Synthesis of water dispersible and biocompatible nanodiamond composite via photocatalytic surface grafting of zwitterionic polymers for intracellular delivery of DOX

As a member of nano-carbon compound, nanodiamonds (ND) with diverse structure, small size and relative low toxicity has been extensively explored for different applications especially as delivery vehicles for drugs. However, surface functionalization of ND with polymers is still required to overcome their poor water dispersibility and improve drug delivery performance. In this work, we reported a simple photocatalytic atom transfer radical polymerization (ATRP) method for surface functionalization of ND by using FeBr3 as the photoredox catalyst. Owing to the introduction of water dispersible 2-methacryloyloxyethyl phosphorylcholine (MPC), resultant NDs-MPC displayed improved water dispersibility and low toxicity. The anticancer agent DOX could be loaded on NDs-MPC efficiently and controlled release from ND-P-DOX complexes. The cell viability and cell imaging results demonstrated that DOX can be transported into cells and maintained its corresponding therapeutic effect. More importantly, as compared with traditional ATRP, photocatalytic ATRP could not only operate under rather mild conditions but also could avoid utilization of expensive and toxic agents. Considered the advantages of photocatalytic ATRP and ND, the method developed in this work could be a promising strategy for fabrication of multifunctional ND-based composites for different applications.

Photoreactive Cytosine-Functionalized Self-Assembled Micelles with Enhanced Cellular Uptake Capability for Efficient Cancer Chemotherapy.

Design, fabrication, and control of photoreactive supramolecular macromers─which are composed of a thermoresponsive polymer backbone and photoreactive nucleobase end-groups─to achieve the desired physical-chemical performance and provide the high efficiency required for chemotherapy drug delivery purposes still present challenges. Herein, a difunctional cytosine-terminated supramolecular macromer was successfully obtained at high yield. UV-irradiation induces the formation of cytosine photodimers within the structure. The irradiated macromer can self-assemble into nanosized spherical micelles in water that possess a number of interesting and unique features, such as desired micellar size and morphology, tunable drug-loading capacity, and excellent structural stability in serum-containing medium, in addition to well-controlled drug-release behaviors in response to changes in environmental temperature and pH; these extremely desirable, rare features are required to augment the functions of polymeric nanocarriers for drug delivery. Importantly, a series of in vitro studies demonstrated that photodimerized cytosine moieties within the drug-loaded micelles substantially enhance their internalization and accumulation inside cells via endocytosis and subsequently lead to induction of massive apoptotic cell death compared with the corresponding nonirradiated micelles. Thus, this newly developed "photomodified" nanocarrier system could provide a potentially fruitful route to enhance the drug delivery performance of nanocages without the need to introduce targeting moieties or additional components.

Correlating Corona Composition and Cell Uptake to Identify Proteins Affecting Nanoparticle Entry into Endothelial Cells.

The formation of the biomolecule corona on the surface of nanoparticles upon exposure to biological fluids critically influences nanocarrier performance in drug delivery. It has been shown that in some cases corona proteins can mediate specific nanoparticle interactions with cell receptors. Within this context, in order to identify corona proteins affecting nanoparticle uptake, in this work, correlation analysis is performed between the corona composition of a panel of silica nanoparticles of different sizes and surface functionalities and their uptake in four endothelial cell types derived from different organs. In this way, proteins that correlate with increased or decreased uptake were identified, and their effects were validated by studying the uptake of nanoparticles coated with a single protein corona and competition studies in brain and liver endothelium. The results showed that precoating nanoparticles with histidine-rich glycoprotein (HRG) alone strongly decreased uptake in both liver and brain endothelium. Furthermore, our results suggested the involvement of the transferrin receptor in nanoparticle uptake in liver endothelium and redirection of the nanoparticles to other receptors with higher uptake efficiency when the transferrin receptor was blocked by free transferrin. These data suggested that changes in the cell microenvironment can also affect nanoparticle uptake and may lead to a different interaction site with nanoparticles, affecting their uptake efficiency. Overall, correlating the composition of the protein corona and nanoparticle uptake by cells allows for the identification of corona molecules that can be used to increase as well as to reduce nanoparticle uptake by cells.

Amino acid functionalized boron nitride nanotubes as an effective nanocarriers for Thiotepa anti-cancer drug delivery

In the current study, the targeted drug delivery performance of the cysteine amino acid functionalized carbon nitride nanotubes (f-C3NNTs) was investigated towards the Thiotepa (TPA) anti-cancer drug through density functional theory (DFT). Also, we carried out calculations on pristine C3NNTs for the sake of better comparison. The results were demonstrating the exothermic and spontaneous nature of the drug absorption onto the nanocarriers. We observed the strongest interactions in f-C3NNTs/TPA complexes. Based on the calculations, when the TPA molecule is adsorbed onto f-C3NNTs, the adsorption distance is shorter, and the adsorption ability and solubility are higher in comparison with its adsorptions onto pristine C3NNTs. All of these complexes are polar, demonstrating their solubility in the aqueous medium. According to quantum molecular descriptors, the reactivity of nano-carriers of f-C3NNTs is more compared to that of pristine C3NNT nano-carriers. Based on the thermodynamic analyses, the interactions between the TPA molecule and f-C3NNTs are exothermic and spontaneous. Therefore, f-C3NNTs can be considered a good candidate for the adsorption of the TPA molecule for drug delivery system in nano-medicine.

Fabrication of Antimicrobial Multilayered Nanofibrous Scaffolds-Loaded Drug via Electrospinning for Biomedical Application.

Nanofibers prepared by biobased materials are widely used in the field of biomedicine, owing to outstanding biocompatibility, biodegradable characters, and excellent mechanical behavior. Herein, we fabricated multilayered nanofibrous scaffolds in order to improve the performance of drug delivery. The composite layer-by-layer scaffolds were incorporated by hydrophobic poly(l-lactic acid) (PLA): polycaprolactone (PCL) and hydrophilic poly(vinyl alcohol) (PVA) nanofibers via multilayer electrospinning. Morphological and structural characteristics of the developed scaffolds measured by scanning electron microscopy (SEM), and transmission electron microscopy (TEM) confirmed smooth and uniform fibers ranging in nanometer scale. The differences in contact angles and Fourier transform infrared spectrum (FTIR) between single-layered PVA nanofibers and multilayered scaffolds verified the existence of PLA: PCL surface. In vitro biodegradable and drug release analysis depicted multilayered scaffolds had good biodegradability and potential for medical application. Due to the model drug incorporation, scaffolds exhibited good antibacterial activity against Escherichia coli and Staphylococcus aureus by the zone of inhibition test. These results revealed that the multilayered scaffolds were proved to be desirable antibacterial materials for biomedical application.

Improving anti-cancer drug delivery performance of magnetic mesoporous silica nanocarriers for more efficient colorectal cancer therapy

BackgroundImproving anti-cancer drug delivery performance can be achieved through designing smart and targeted drug delivery systems (DDSs). For this aim, it is important to evaluate overexpressed biomarkers in the tumor microenvironment (TME) for optimizing DDSs.Materials and methodsHerein, we designed a novel DDS based on magnetic mesoporous silica core–shell nanoparticles (SPION@MSNs) in which release of doxorubicin (DOX) at the physiologic pH was blocked with gold gatekeepers. In this platform, we conjugated heterofunctional polyethylene glycol (PEG) onto the outer surface of nanocarriers to increase their biocompatibility. At the final stage, an epithelial cell adhesion molecule (EpCAM) aptamer as an active targeting moiety was covalently attached (Apt-PEG-Au@NPs-DOX) for selective drug delivery to colorectal cancer (CRC) cells. The physicochemical properties of non-targeted and targeted nanocarriers were fully characterized. The anti-cancer activity, cellular internalization, and then the cell death mechanism of prepared nanocarriers were determined and compared in vitro. Finally, tumor inhibitory effects, biodistribution and possible side effects of the nanocarriers were evaluated in immunocompromised C57BL/6 mice bearing human HT-29 tumors.ResultsNanocarriers were successfully synthesized with a mean final size diameter of 58.22 ± 8.54 nm. Higher cytotoxicity and cellular uptake of targeted nanocarriers were shown in the EpCAM-positive HT-29 cells as compared to the EpCAM-negative CHO cells, indicating the efficacy of aptamer as a targeting agent. In vivo results in a humanized mouse model showed that targeted nanocarriers could effectively increase DOX accumulation in the tumor site, inhibit tumor growth, and reduce the adverse side effects.ConclusionThese results suggest that corporation of a magnetic core, gold gatekeeper, PEG and aptamer can strongly improve drug delivery performance and provide a theranostic DDS for efficient CRC therapy.Graphic abstract

Acid-triggered degradable diblock poly(doxorubicin)-polyethylene glycol polyprodrug with doxorubicin as structural unit for tumor intracellular delivery

Polyprodrugs, in which drug was used as the structural unit by linking with each other via the dynamic covalent bonds in the main chain, are expected to endow excellent drug delivery performance. Here, acid-triggered degradable diblock polyprodrug, poly(doxorubicin)-polyethylene glycol (PDOX-PEG), was designed with DOX as structural unit alternately linked with acid-labile hydrazone and maleic amide groups, by the polycondensation of DOX-based dimers (D-DOXADH or D-DOXMAH) with PEGylated dimer (DOX-ADH-DOX-PEG) as end capping agent. The optimized PDOX-PEG, which was synthesized with D-DOXADH and the PEGylated dimer at a feeding ratio of 10%, possessed a high Mn of 3.1 × 104 g/mol with a high DOX content of 75.42%. It could easily self-assemble into near spherical nanoparticles with average hydrodynamic diameter of 135 nm. They showed excellent pH-triggered sustained drug release owing to the acid-triggered degradation of the polyprodrug block in the tumor intracellular microenvironment, with low premature drug leakage of 4.39 % within 60 h. The MTT results indicated the enhanced antitumor efficacy of the proposed PDOX-PEG nanoparticles than free DOX. The results demonstrated the promising potential of the proposed acid-triggered degradable diblock PDOX-PEG polyprodrug for tumor treatment.

Evaluation of Aerosol Drug Delivery Options during Adult Mechanical Ventilation in the COVID-19 Era.

Drug delivery devices used for aerosol therapy during mechanical ventilation to ease the symptoms of respiratory diseases provide beneficial treatment but can also pose challenges. Reflecting the significant changes in global guidance around aerosol usage and lung-protective ventilation strategies, seen in response to the COVID-19 pandemic, for the first time, we describe the drug delivery performance of commonly used devices under these conditions. Here, vibrating mesh nebuliser (VMN), jet nebuliser (JN) and pressurised metered-dose inhaler (pMDI) performance was assessed during simulated adult mechanical ventilation. Both standard test breathing patterns and those representatives of low tidal volume (LTV) ventilation with concurrent active and passive humidification were investigated. Drug delivery using a VMN was significantly greater than that with a JN and pMDI for both standard and LTV ventilation. Humidification type did not affect the delivered dose across all device types for standard ventilation. Significant variability in the pMDI dosing was evident, depending on the timing of actuation and the adapter type used. pMDI actuation synchronised with inspiration resulted in a higher delivered drug dose. The type of adapter used for pMDI actuation influenced drug delivery, with the highest dose observed using the CombiHaler.

Co-delivery of nanoparticle and molecular drug by hollow mesoporous organosilica for tumor-activated and photothermal-augmented chemotherapy of breast cancer

BackgroundIn comparison with traditional therapeutics, it is highly preferable to develop a combinatorial therapeutic modality for nanomedicine and photothermal hyperthermia to achieve safe, efficient, and localized delivery of chemotherapeutic drugs into tumor tissues and exert tumor-activated nanotherapy. Biocompatible organic–inorganic hybrid hollow mesoporous organosilica nanoparticles (HMONs) have shown high performance in molecular imaging and drug delivery as compared to other inorganic nanosystems. Disulfiram (DSF), an alcohol-abuse drug, can act as a chemotherapeutic agent according to its recently reported effectiveness for cancer chemotherapy, whose activity strongly depends on copper ions.ResultsIn this work, a therapeutic construction with high biosafety and efficiency was proposed and developed for synergistic tumor-activated and photothermal-augmented chemotherapy in breast tumor eradication both in vitro and in vivo. The proposed strategy is based on the employment of HMONs to integrate ultrasmall photothermal CuS particles onto the surface of the organosilica and the molecular drug DSF inside the mesopores and hollow interior. The ultrasmall CuS acted as both photothermal agent under near-infrared (NIR) irradiation for photonic tumor hyperthermia and Cu2+ self-supplier in an acidic tumor microenvironment to activate the nontoxic DSF drug into a highly toxic diethyldithiocarbamate (DTC)-copper complex for enhanced DSF chemotherapy, which effectively achieved a remarkable synergistic in-situ anticancer outcome with minimal side effects.ConclusionThis work provides a representative paradigm on the engineering of combinatorial therapeutic nanomedicine with both exogenous response for photonic tumor ablation and endogenous tumor microenvironment-responsive in-situ toxicity activation of a molecular drug (DSF) for augmented tumor chemotherapy.Graphical abstract

Targeted pulmonary drug delivery in coronavirus disease (COVID-19) therapy: A patient-specific in silico study based on magnetic nanoparticles-coated microcarriers adhesion

Since the beginning of the COVID-19 pandemic, nearly most confirmed cases develop respiratory syndromes. Using targeted drug delivery by microcarriers is one of the most important noteworthy methods for delivering drugs to the involved bronchi. This study aims to investigate the performance of a drug delivery that applies microcarriers to each branch of the lung under the influence of a magnetic field. The results show that by changing the inlet velocity from constant to pulsatile, the drug delivery performance to the lungs increases by ∼31%. For transferring the microcarriers to the right side branches (LUL and LLL), placing the magnet at zero height and ∼30° angle yields the best outcome. Also, the microcarriers' delivery to branch LUL improves by placing the magnet at LUL-LLL bifurcation and the angle of ∼30°. It was observed that dense (9300[kgm3]) microcarriers show the best performance for delivering drugs to LLL and RLL&RML branches. Also, low-density (1000[kgm3]) microcarriers are best for delivering drugs to LUL and RUL branches. The findings of this study can improve our understanding of different factors, such as inlet velocity, the magnet’s position, and the choice of microcarrier – that affect drug delivery to the infected parts of the lung.

On the potential of all-boron fullerene B40 as a carrier for anti-cancer drug nitrosourea

The potential application of all-boron fullerene B40 as a drug carrier for anti-cancer nitrosourea (NU) has been explored by the means of density functional theory (DFT). Our results reveal that the NU drug tends to combine with the corner boron atom of B40 cage via its oxygen and nitrogen atoms with a moderate adsorption energy of −25.18 kcal/mol. Herein, the newly formed B-O and B-N bonds are proved to be strong polar covalent bonds by atoms in molecules (AIM) theory, localized molecular orbital (LMO), and electron localization function (ELF) analyses. A short recovery time of 52 s is predicted for the NU desorption process at 310.15 K, indicating that the desorption of NU from B40 is easy under body temperature. Moreover, it is found that B40 can simultaneously adsorb up to five NU drugs, exhibiting a high loading capacity. Finally, the substituent effect of C, N, Al, and Ga atoms on the drug delivery performance of this B40 nanocage has been considered. Our results not only suggest that B40 has a great potential to be used in drug delivery, but also signify that the substituent effect of foreign atoms can be employed to modulate the drug adsorption performance of B40.

Hydrogen Bond Strength-Mediated Self-Assembly of Supramolecular Nanogels for Selective and Effective Cancer Treatment.

This study provides a significant contribution to the development of multiple hydrogen-bonded supramolecular nanocarrier systems by demonstrating that controlling the hydrogen bond strength within supramolecular polymers represents a crucial factor to tailor the drug delivery performance and enhance the effectiveness of cancer therapy. Herein, we successfully developed two kinds of poly(ethylene glycol)-based telechelic polymers Cy-PEG and UrCy-PEG having self-constituted double and quadruple hydrogen-bonding cytosine (Cy) and ureido-cytosine (UrCy) end-capped groups, respectively, which directly assemble into spherical nanogels with a number of interesting physical characteristics in aqueous solutions. The UrCy-PEG nanogels containing quadruple hydrogen-bonded UrCy dimers exhibited excellent long-term structural stability in a serum-containing biological medium, whereas the double hydrogen-bonded Cy moieties could not maintain the structural integrity of the Cy-PEG nanogels. More importantly, after the drug encapsulation process, a series of in vitro experiments clearly confirmed that drug-loaded UrCy-PEG nanogels induced selective apoptotic cell death in cancer cells without causing significant cytotoxicity to healthy cells, while drug-loaded Cy-PEG nanogels exerted nonselective cytotoxicity toward both cancer and normal cells, indicating that increasing the strength of hydrogen bonds in nanogels plays a key role in enhancing the selective cellular uptake and cytotoxicity of drugs and the subsequent induction of apoptosis in cancer cells.

Hyaluronic Acid-Functionalized Nanomicelles Enhance SAHA Efficacy in 3D Endometrial Cancer Models.

Simple SummaryOne of the major limitations to cancer therapies are the side effects caused by the drug interacting with any tissue in the body. There is often a balance between patient health and effectively treating the disease. To by-pass this balancing act nanoparticles are being used to deliver therapeutics straight to the tumors, acting as “Trojan Horses”. Endometrial cancers are known to have more of the cell surface protein CD44 than healthy tissues. Here, to efficiently target endometrial cancer, hyaluronic acid, which naturally binds to the CD44 protein was attached to the surface of nanoparticles and tested on microtissues or spheroids to better model a tumor and understand drug delivery performance. We show that our hyaluronic acid-nanoparticle formulations improve drug effects and interact with the cancer cells more than without this targeting agent.Histone Deacetylase (HDAC) enzymes are upregulated in cancer leading to the development of HDAC inhibiting compounds, several of which are currently in clinical trials. Side effects associated with toxicity and non-specific targeting indicate the need for efficient drug delivery approaches and tumor specific targeting to enhance HDAC efficacy in solid tumor cancers. SAHA encapsulation within F127 micelles functionalized with a surface hyaluronic acid moiety, was developed to target endometrial cancer cells expressing elevated levels of CD44. In vitro viability and morphology analyses was conducted in both 2D and 3D models to assess the translational potential of this approach. Encapsulation enhanced SAHA delivery and activity, demonstrating increased cytotoxic efficacy in 2D and 3D endometrial cancer models. High-content imaging showed improved nanoparticle internalization in 2D and CD44 enhanced penetration in 3D models. In addition, the nano-delivery system enhanced spheroid penetration resulting in cell growth suppression, p21 associated cell cycle arrest, as well as overcoming the formation of an EMT associated phenotype observed in free drug treated type II endometrial cancer cells. This study demonstrates that targeted nanoparticle delivery of SAHA could provide the basis for improving its efficacy in endometrial cancer. Using 3D models for endometrial cancer allows the elucidation of nanoparticle performance and CD44 targeting, likely through penetration and retention within the tumor model.

Microwave-triggered ionic liquid-based hydrogel dressing with excellent hyperthermia and transdermal drug delivery performance

Phototherapy still lacks effectiveness in treating tissue infections due to poor penetration depth of light and laser-induced non-specific thermal diffusion. Microwave thermal therapy (MWTT) is advantageous as characterized by strong tissue penetration, and higher heating rate. In addition, transdermal delivery of drugs helps in the treatment of tissue infections. Herein, we present an all-in-one MW-therapeutic hydrogel for eradicating bacterial infections with transdermal drug delivery. A microwave-responsive ionic liquid (IL), i.e., vinylbenzyl trimethylammonium chloride (VBTMACl), and a transdermal-enhancer IL, i.e., [2-(methacryloyloxy)ethyl] trimethylammonium chloride (ChMACl), are copolymerized with acrylic acid (AA) to form the hydrogel VACPHs. Polyvinylpyrrolidone (PVP) is incorporated with VACPHs to improve their mechanical stability. The model drug levofloxacin (LEVO) is subsequently loaded into the hydrogel, and the VACPHs-LEVO shows strong antibacterial effect. It is attributed to the efficient microwaveocaloric therapy of VBTMACl and enhanced transdermal antibiotic delivery by ChMACl. The drug delivery hydrogel developed in this research exhibits excellent performance for the treatment of deep tissue infections.

PH/H2O2 Dual-Responsive Chiral Mesoporous Silica Nanorods Coated with a Biocompatible Active Targeting Ligand for Cancer Therapy.

Nano-drug delivery systems (nano-DDSs) with an existing specific interaction to tumor cells and intelligent stimulus-triggered drug delivery performance in a tumor microenvironment (TME) remain hotspots for effective cancer therapy. Herein, multifunctional pH/H2O2 dual-responsive chiral mesoporous silica nanorods (HA-CD/DOX-PCMSRs) were creatively constructed by first grafting phenylboronic acid pinacol ester (PBAP) onto the amino-functioned nanorods, then incorporating doxorubicin (DOX) into the mesoporous structure, and finally coating with the cyclodextrin-modified hyaluronic acid conjugate (HA-CD) through a weak host-guest interaction. Under a physiological environment, the gatekeeper CD could avoid the premature leakage of DOX and minimize the side effects to normal cells. After the uptake by the tumor cells, the H2O2-sensitive moieties of PBAP were exposed and a small amount of DOX was leaked along with the shift of the supramolecular switch HA-CD under the acidic condition. Notably, the self-supplying H2O2 mediated by the released DOX in turn accelerated the PBAP disintegration, further promoted the rapid release of DOX, and increased the DOX accumulation in tumor regions. Innovatively, this nano-DDS could simultaneously achieve the tumor-targeting ability via CD44 receptor-mediated endocytosis and pH/H2O2 dual responsiveness activated by the TME and hence exhibited superior antitumor efficacy. Furthermore, HA acting as the hydrophilic shell could improve the biocompatibility of this nano-DDS.

Synthesis, crystal structure, DFT studies, Hirshfeld surface analysis and drug delivery performance of bis(2-chloro-4,6-diaminopyrimidine)copper(II)-dichloride

The new single crystal, bis(2-chloro-4,6-diaminopyrimidine)-copper(II)-dichloride [CDPCD] compound was synthesized. The crystal structure of the compound was solved by the single crystal X-ray diffraction method. CDPCD has a=6.3334(9) Å, b=6.9914 (10)Å, c=8.9901(12)Å, α=78.127(11)°, β=86.853(11)°, γ=67.307(10)° and Z=1 parameters and is crystallized in the space group P-1 in the triclinic crystal system. Complete vibration assignments of CDPCD in gas phase and experimental frequencies are reported together with the scaled force constants. The optimized geometric parameters and frequency values were theoretically calculated using DFT/B3LYP method with LANL2DZ basis set. The XRD single crystal measurement parameters are good agreed with the optimized parameters. Molecular orbital surfaces and molecular electrostatic potential properties were measured at B3LYP/LANL2DZ level. Hirshfeld surface and fingerprint drawings were obtained to explain the intermolecular interactions of the crystal structure. The most important contributions for the crystal packing are from Cl…H/H…Cl (38.7%), H…H (17.9%) and N…H/H…N (14.8%) interactions. In addition, the molecule was tested by MTT test to determine the apoptosis and necrosis by cytotoxicity and double staining method. For the MTT test [MTT: (3,4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], the tetrazolium salt was used. In different percentages of the compound, apoptotic necrotic index ratios of L929 fibroblasts and MCF-7 cells decreased. Bilateral staining method was used to evaluate the cells that had undergone apoptosis and necrosis of FITC (480-520nm wavelength). Apoptotic and necrotic index results of L929 fibroblasts and MCF-7 cells decreased as the amount of concentration decreased.

Water-Soluble Blue Fluorescent Nonconjugated Polymer Dots from Hyaluronic Acid and Hydrophobic Amino Acids.

Fluorescent polymers have been increasingly investigated to improve their water solubility and biocompatibility to enhance their performance in drug delivery and theranostic applications. However, the environmentally friendly synthesis and dual functionality of such systems remain a challenge due to the complicated synthesis of conventional fluorescent materials. Herein, we generated a novel blue fluorescent polymer dot through chemical conjugation of hydrophobic amino acids to hyaluronic acid (HA) under one-pot green chemistry conditions. These nonconjugated fluorescent polymer dots (NCPDs) are water soluble, nontoxic to cells, have high fluorescence quantum yield, and can be used for in vitro bioimaging. HA-derived NCPDs exhibit excitation wavelength-dependent fluorescent properties. In addition, the NCPDs also show enhanced doxorubicin loading and delivery in naive and drug-resistant breast cancer cells in 2D and 3D tumor cellular systems. These results demonstrate the potential for successful synthetic scale-up and applications for HA-derived NCPDs.