Polymeric Nanocomplex Research Articles

PH-tailored delivery of a multitarget anticancer benzimidazole derivative using a PEGylated β-cyclodextrin-curcumin functionalized nanocomplex

In this study, we aimed to enhance the bioavailability of a benzimidazole derivative with potent anticancer potential through a nano-based approach. Benzimidazole-loaded polyethylene glycol-β-cyclodextrin–functionalized curcumin nanocomplex (BMPE-Cur) was prepared and characterized for its physicochemical properties and drug release profiles under different pH conditions. In addition, the biological activities of the nanocomplex including antioxidant potentials and pro-apoptogenic properties, against HepG2, PC3, and the chemo-resistant MCF-7-ADR cell lines relative to the normal Wi-38 cell line were in vitro assessed and compared with those of the free benzimidazole compound. In addition to FTIR, XRD, and NMR spectral studies, a polymeric nanocomplex with an average particle size of 467.7 nm and high stability was successfully developed, as indicated by the negative zeta potential (−28.24 mV). The nanocomplex also showed prolonged pH-sensitive sustained drug release under conditions that replicated the tumor's extra/intracellular pH. The formulated nanocomplex also demonstrated potent radical scavenging capacity owing to the inclusion of curcumin, a known radical quencher. In addition, compared with the free compound, BMPE-Cur induced DNA fragmentation-driven cell cycle arrest in HepG2, PC3, and MCF-7-ADR cells at the G1/S, G1 & S phases; respectively, with remarkable selectivity. In conclusion, the newly formulated BMPE-Cur nanocomplex represents an attractive multitarget anticancer candidate.

Synergistic antitumor immune response mediated by paclitaxel-conjugated nanohybrid oncolytic adenovirus with dendritic cell therapy.

Dendritic cell (DC)-based vaccines have emerged as a promising strategy in cancer immunotherapy due to low toxicity. However, the therapeutic efficacy of DC as a monotherapy is insufficient due to highly immunosuppressive tumor environment. To address these limitations of DC as immunotherapeutic agent, we have developed a polymeric nanocomplex incorporating (1) oncolytic adenovirus (oAd) co-expressing interleukin (IL)-12 and granulocyte-macrophage colony-stimulating factor (GM-CSF) and (2) arginine-grafted bioreducible polymer with PEGylated paclitaxel (APP) to restore antitumor immune surveillance function in tumor milieu and potentiate immunostimulatory attributes of DC vaccine. Nanohybrid complex (oAd/APP) in combination with DC (oAd/APP+DC) induced superior expression level of antitumor cytokines (IL-12, GM-CSF, and interferon gamma) than either oAd/APP or DC monotherapy in tumor tissues, thus resulting in superior intratumoral infiltration of both endogenous and exogenous DCs. Furthermore, oAd/APP+DC treatment led superior migration of DC to secondary lymphoid organs, such as draining lymph nodes and spleen, in comparison with either monotherapy. Superior migration profile of DCs in oAd/APP+DC treatment group resulted in more prolific activation of tumor-specific T cells in these lymphoid organs and greater intratumoral infiltration of T cells. Additionally, oAd/APP+DC treatment led to lower subset of tumor infiltrating lymphocytes and splenocytes being immunosuppressive regulatory T cells than any other treatment groups. Collectively, oAd/APP+DC led to superior induction of antitumor immune response and amelioration of immunosuppressive tumor microenvironment to elicit potent tumor growth inhibition than either monotherapy.

Restoring physiological parameters of the pancreas and kidney through treatment with a polymeric nano-formulation of C-peptide and lisofylline combination in diabetic nephropathy.

Diabetic nephropathy (DN) is a progressive kidney disorder that develops as a complication of diabetes due to long-term exposure to elevated blood glucose levels (BGLs). In this case, an intervention of therapeutic moieties is needed to target the specific elements involved in diabetes to prevent/delay the deterioration of kidney function. Therefore, the present study focused on designing and evaluating a potent nano-formulation of a combination of C-peptide (CPep) and the anti-diabetic drug lisofylline (LSF) to prevent streptozotocin (STZ)-induced DN. As a strategic intervention, an LSF-oleic acid prodrug (LSF-OA) was initially synthesized and further encapsulated in an in-house-synthesized cationic polymer [(mPEG-b-P(CB-{g-DMDP}-co-LA)); mPLM] to prepare polymeric nano-complexes of CPep via electrostatic interaction, possessing a size of 218.6 ± 14.4 nm and zeta potential of +5.2 mV together with stability for 30 days at 25 °C. mPLM-LSF-OA-CPep nanoparticles demonstrated hemocompatibility with RBCs and exhibited potent anti-oxidant activity by reducing nitrite levels, inducing the release of anti-oxidant GSH and protecting metabolically stressed rat kidneys and murine insulinoma cells from apoptosis. In vivo pharmacokinetics depicted an increase in t½ and mean residence time in rats, which further improved the BGL and renal conditions and reduced plasma IL-6 and TNF-α levels in the STZ-induced DN animal model when treated with mPLM-LSF-OA-CPep compared to free LSF and CPep. Moreover, an increase in the plasma insulin level and detection of proliferative marker cells in pancreatic islets suggested the regeneration of β-cells in diabetic animals.

Fabrication of poly(β-amino ester) and hyaluronic acid based pH responsive nanocomplex as an antibiotic release system

World Health Organization (WHO) warns about antimicrobial resistance (AMR) considered as the most serious threats to global health, food security, and development. There are various efforts for elimination of this serious issue. These efforts include education of individuals, new policies, development of new antimicrobials and new materials for effective delivery. Novel drug delivery systems with ability of local and on-demand delivery are one of the promising approaches for prevention of AMR. In this regard, a pH-responsive antibiotic delivery system based on pH-responsive poly(β-amino ester) (PBAE) and enzyme responsive hyaluronic acid (HA). The polymeric nanocomplexes were obtained via electrostatic complexation of PBAE and HA in the presence of a model antibiotics, colistin and vancomycin. The particle sizes at pH 7.4 were determined in the range of 131–730 nm and 120–400 nm by DLS and STEM, respectively. When pH was switched from 7.4 to 5.5, the hydrodynamic diameter increased 2.5–32 fold. The drug release performances were tested using FITC-labeled antibiotics via fluorescence spectroscopy. The nanocomplexes released the drugs more at pH 5.5 compared to pH 7.4. Antibacterial activity of the system was evaluated on various bacteria. The nanocomplex loaded with the antibiotics exhibited significantly greater efficacy against E. coli and S. aureus.

The anti-cancer effect of chitosan/resveratrol polymeric nanocomplex against triple-negative breast cancer; an in vitro assessment.

Herein, the authors synthesised chitosan nanoparticles (Cs NPs) as a resveratrol (RSV) carrier and evaluated their efficacy in stimulating apoptosis in MDA-MB 231 cells. Blank (Cs NPs) and RSV- Cs NPs (RSV-Cs NPs) were synthesised via ionic gelation and characterised by using fourier-transform infrared spectroscopy (FTIR), Scanning electron microscope, dynamic light scattering/Zeta potential and RSV release. MDA-MB 231 cells were treated with RSV, Cs NPs and RSV-Cs NPs (24, 48, and 72h), followed by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Cell toxicity was evaluated using lactate dehydrogenase assay, and real-time polymerase chain reaction was performed to explore apoptosis induction. FTIR spectra confirmed the NPs via the formation of cross-linking bonds. Cs and RSV-Cs NPs sizes were about 75 and 198nm with 14 and 24mV zeta potentials. The RSV entrapment efficiency was 52.34±0.16%, with an early rapid release followed by a sustained manner. Cs and RSV-Cs NPs inhibited cell proliferation at lower concentrations and IC50 values. RSV-Cs NPs had the most cytotoxic effect and stimulated intrinsic apoptotic pathway, indicated by increased Bcl-2-associated x (BAX), BAX/Bcl-2 ratio, P53 expressions, reduced Bcl-2 and upregulated caspases 3, 8 and 9. RSV-Cs NPs have a great potential to suppress invasive breast cancer cell proliferation by targeting mitochondrial metabolism and inducing the intrinsic apoptotic pathway.

Protonated cross-linkable nanocomposite coatings with outstanding underwater superoleophobic and anti-viscous oil-fouling properties for crude oil/water separation

Superhydrophilic/underwater superoleophobic coatings that effectively prevent viscous oil contamination have been of considerable interest for the great potential in oil spill remediation and oilfield wastewater treatment. In the present work, a protonated cross-linkable nanocomposite coating with robust underwater superoleophobicity and intensified hydration capability is proposed through the synthesis of active polymeric nanocomplex (PNC), cross-linking reaction between PNC and hydrophilic chitosan (CS), and final protonation to further improve water affinity. Benefiting from the hierarchical structure and strong hydration capability induced by electrostatic interactions and hydrogen bondings, the nanocomposite coating coated textile exhibits excellent superhydrophilicity (within 0.28 s with water contact angle reaching 0°), underwater superoleophobicity (underwater crude oil contact angle at 160°), and ultralow oil adhesion even to highly viscous silicone oil. Moreover, the nanocomposite coating presents a robust chemical resistance, mechanical tolerance, and storage stability. Simultaneously, the nanocomposite coating adapts well to various porous substrates (e.g., stainless steel mesh and Ni sponge) with great anti-oil-fouling and self-cleaning performances. Importantly, the coating coated textile is successfully applied in crude oil/water separation with excellent efficiency and repeatability. The findings conceivably stand out as a new methodology to fabricate superhydrophilic/underwater superoleophobic materials with outstanding anti-viscous oil-fouling property for practically treating oily wastewater.

Combinatorial cetuximab targeted polymeric nanocomplexes reduce PRC1 level and abrogate growth of metastatic hepatocellular carcinoma in vivo with efficient radionuclide uptake

Hepatocellular carcinoma (HCC) is the most aggressive form of cancer with poor drug responses. Developing an effective drug treatment remains a major unmet clinical need for HCC. We report a comprehensive study of combinatorial Cetuximab (Cet) targeted polymeric poly(D, L-lactide-co-glycolide)-b-poly(ethylene glycol) nanocomplexes delivery of Combretastatin A4 (CA4) and 2-Methoxyestradiol (2ME) (Cet-PLGA-b-PEG-CA4 NP + Cet-PLGA-b-PEG-2ME NP) against metastatic HCC in SCID mice. 125I-Cet-PLGA-b-PEG NP showed potent accumulation and retention in HCC tumors with longer circulation time up to 48 h (18 ± 1.0% ID/g, P < .0001). Combinatorial treatment with targeted polymeric nanocomplexes presented significant tumor growth inhibition (85%, P < .0001) than the free drug combinatorial counterpart, effectively inhibited orthotopic HCC and prevented lung metastasis. Combinatorial nanocomplexes treatment significantly blocked PRC1, a novel target of therapeutic response against HCC. Thus, the combinatorial cetuximab-targeted polymeric nanocomplexes possess superior antitumor activity against metastatic HCC and provide supports for the clinical translation ahead.

Polymeric nanocomplexes based on polyaluminophenylsiloxanes

Polymeric nanocomplexes based on polyaluminophenylsiloxanes

Abstract 13: High-Throughput, Non-Invasive Raman Spectroscopy of Anticancer Nanomedicine for Liver Cancer Therapeutic Intervention

Abstract Purpose: Liver cancer remains one of the most difficult to treat, heterogeneous forms of cancer with poor prognosis. Available current therapies face many limitations. Raman spectroscopy is a promising platform for clinical drug development and surgical interventions for improved patient outcomes. Herein, we present a new insight with a rapid, non-destructive, non-invasive Raman spectroscopy modality based molecular signatures unique to anticancer nanomedicine signifying distinct stratification in liver cancer treated tissues of SCID mice. Methods: The therapeutic intervention was investigated using a high-throughput Raman spectroscopy in ex vivo liver tissues treated with combinatorials; targeted and non-targeted polymeric nanocomplexes encapsulated microtubule inhibitors against metastatic liver cancer in SCID mice. Principal Component Analysis (PCA), Linear Discriminate Analysis (LDA) for multivariate data analysis, and cross validation method was used to extrapolate the high throughput Raman based treatment efficiency study in ex vivo liver tissues. Results: Raman spectral signatures obtained by Raman spectroscopy of liver tissue samples of healthy normal liver versus liver cancer cohorts exhibited complete discrimination of healthy ones from the affected diseased counterparts with high accuracy classification. This could be useful as a liver cancer diagnosis tool. Peculiar Raman profiles with distinct stratification of targeted anticancer nanomedicine combinatorials treated cohort were observed. Interestingly, apoptotic lipid bodies and amide I was the prominent features revealed in anticancer nanomedicine combinatorials treatment cohorts. Conclusion: Our approach is a significant advancement for unique Raman molecular signatures-based targeted anticancer nanomedicine combinatorials therapeutic intervention for liver cancer in tissues. Clinical translation of this proposed modality would define Raman based rapid, high-throughput platform for the clinical drug development and monitoring against liver cancer remains warranted. Citation Format: Radhika Poojari, Mithila Bhujbal, Arti Hole, Murali Krishna Chilakapati. High-Throughput, Non-Invasive Raman Spectroscopy of Anticancer Nanomedicine for Liver Cancer Therapeutic Intervention [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 13.

Distinct stratification of normal liver, hepatocellular carcinoma (HCC), and anticancer nanomedicine-treated- tumor tissues by Raman fingerprinting for HCC therapeutic monitoring

Hepatocellular carcinomas (HCCs) are highly vascularized neoplasms with poor prognosis. Nanomedicine possesses great potential to deliver therapeutics and diagnostics. The new aspect of this study is that we have monitored, for the first time, the Raman responses to microtubule targeted vascular disrupting agents (MTVDA), MTVDA encapsulated non-targeted, and targeted cetuximab polymeric nanocomplexes delivery of combinatorial therapeutics in HCC tumor tissues of mice. Biochemical differences majorly demarcated apoptotic lipid bodies, and characteristic amide-I features. HCC tumor and healthy liver tissues could be stratified. Raman spectroscopy served as an excellent, rapid, sensitive and cost-effective approach for anticancer nanomedicine distinct stratification of MTVDA encapsulated targeted cetuximab polymeric nanocomplex combinatorials, a significant potential for HCC therapeutic monitoring.

141 Poster - A comprehensive analysis of cetuximab combinatorial polymeric nanocomplexes with potent radionuclide uptake to combat metastatic liver cancer

Background: Herein, we have determined the anticancer effects of Cetuximab targeted combinatorial polymeric nanocomplexes comprising either combretastatin A4 or methoxyestradiol in ectopic and orthotopic metastatic liver cancer SCID mice models.

Non-viral gene delivery of HIF-1α promotes angiogenesis in human adipose-derived stem cells

Stable and mature vascular formation is a current challenge in engineering functional tissues. Transient, non-viral gene delivery presents a unique platform for delivering genetic information to cells for tissue engineering purposes and to restore blood flow to ischemic tissue. The formation of new blood vessels can be induced by upregulation of hypoxia-inducible factor-1α (HIF-1), among other factors. We hypothesized that biodegradable polymers could be used to efficiently deliver the HIF-1α gene to human adipose-derived stromal/stem cells (hASCs) and that this treatment could recruit an existing endogenous endothelial cell population to induce angiogenesis in a 3D cell construct in vitro. In this study, end-modified poly(β-amino ester) (PBAE) nanocomplexes were first optimized for transfection of hASCs and a new biodegradable polymer with increased hydrophobicity and secondary amine structures, N'-(3-aminopropyl)-N,N-dimethylpropane-1,3-diamine end-modified poly(1,4-butanediol diacrylate-co-4-amino-1-butanol), was found to be most effective. Optimal PBAE nanocomplexes had a hydrodynamic diameter of approximately 140 nm and had a zeta potential of 30 mV. The PBAE polymer self-assembled with HIF-1α plasmid DNA and treatment of hASCs with these nanocomplexes induced 3D vascularization. Cells transfected with this polymer-DNA complex were found to have 106-fold upregulation HIF-1α expression, an approximately 2-fold increase in secreted VEGF, and caused the formation of vessel tubules compared to an untransfected control. These gene therapy biomaterials may be useful for regenerative medicine. Statement of SignificanceNot only is the formation of stable vasculature a challenge for engineering human tissues in vitro, but it is also of valuable interest to clinical applications such as peripheral artery disease. Previous studies using HIF-1α to induce vascular formation have been limited by the necessity of hypoxic chambers. It would be advantageous to simulate endogenous responses to hypoxia without the need for physical hypoxia. In this study, 3D vascular formation was shown to be inducible through non-viral gene delivery of HIF-1α with new polymeric nanocomplexes. A biodegradable polymer N'-(3-aminopropyl)-N,N-dimethylpropane-1,3-diamine end-modified poly(1,4-butanediol diacrylate-co-4-amino-1-butanol) demonstrates improved transfection of human adipose-derived stem cells. This nanobiotechnology could be a promising strategy for the creation of vasculature for tissue engineering and clinical applications.

An inflammation self-adaptive nanocarrier for highly efficient gene therapy

Inflammation represents a real micromilieu of many diseases as well as the actual application environment of nanocarriers. However, few studies have focused on the influence of the inflammatory environment on the effects of nanoparticle delivery. Herein, a novel inflammation self-adaptive nanocarrier is designed and fabricated by attaching the ascorbyl palmitate (AP) onto the surface of gene-entrapped polymeric nanocomplexes through the formation of phenylboronate bond. In vitro and in vivo studies demonstrate that the introduction of AP enhances considerably the accumulation of entrapped gene in inflammation and facilitates the intracellular uptake of gene-loading nanoparticles. Meanwhile, the gene transfection efficiency of DNA and in vivo gene therapy of nanocomplexes under an inflammation stimulus is significantly enhanced. Hence, our delicate design concept opens up a new pathway to develop an inflammation self-adaptive drug delivery system for precise drug/gene delivery and therapy.

A Scalable Chemical Approach for the Synthesis of a Highly Tolerant and Efficient Oil Absorbent.

In the past, bio-inspired extreme water repellent property has been strategically embedded on commercially available sponges for developing selective oil absorbents. However, most of the reported materials lack physical and chemical durability, limiting their applicability at practically harsh settings. Herein, a stable dispersion of polymeric nanocomplexes was exploited to achieve a chemically reactive coating on the highly compressible melamine foam. A superhydrophobic melamine foam (SMF) was achieved after post-covalent modification of the reactive coating through 1,4-conjugate addition reaction at ambient conditions. The durability of the embedded extreme water repellent property in the as-modified melamine foam has been elaborately demonstrated through exposing it to severe physical manipulations, chemically harsh aqueous media including pH 1, pH 12, surfactant contaminated water, river water, seawater and prolonged UV irradiation. Thus, the highly tolerant SMF was utilized as an efficient oil absorbent wherein oils of varying densities could be selectively recovered from an oil/water interface with high (e.g., 137 g g-1 for chloroform and 83 g g-1 for diesel) oil absorption capacity. Moreover, the selective oil absorption capacity of the as-synthesized material remained unaffected at practically relevant severe chemical and physical settings, and the extreme water repellency of the material remained unaltered even after repetitive (at least 50 cycles) use for oil/water separation.

Redox-Responsive Polymeric Nanocomplex for Delivery of Cytotoxic Protein and Chemotherapeutics.

Responsive delivery of anticancer proteins into cells is an emerging field in biological therapeutics. Currently, the delivery of proteins is highly compromised by multiple successive physiological barriers that reduce the therapeutic efficacy. Hence, there is a need to design a robust and sustainable nanocarrier to provide suitable protection of proteins and overcome the physiological barriers for better cellular accumulation. In this work, polyethylenimine (PEI) cross-linked by oxaliplatin(IV) prodrug (oxliPt(IV)) was used to fabricate a redox-responsive nanocomplex (PEI-oxliPt(IV)@RNBC/GOD) for the delivery of a reactive oxygen species-cleavable, reversibly caged RNase A protein (i.e., RNase A nitrophenylboronic conjugate, RNBC) and glucose oxidase (GOD) in order to realize efficient cancer treatment. The generation of hydrogen peroxide by GOD can uncage and restore the enzymatic activity of RNBC. On account of the responsiveness of the nanocomplex to highly reducing cellular environment, it would dissociate and release the protein and active oxaliplatin drug, causing cell death by both catalyzing RNA degradation and inhibiting DNA synthesis. As assessed by the RNA degradation assay, the activity of the encapsulated RNBC was recovered by the catalytic production of hydrogen peroxide from GOD and glucose substrate overexpressed in cancer cells. Monitoring of the changes in nanoparticle size confirmed that the nanocomplex could dissociate in the reducing environment, with the release of active oxaliplatin drug and protein. Confocal laser scanning microscopy (CLSM) and flow cytometry analysis revealed highly efficient accumulation of the nanocomplex as compared to free native proteins. In vitro cytotoxicity experiments using 4T1 cancer cells showed ∼80% cell killing efficacy, with highly efficient apoptosis induction. Assisted by the cationic polymeric carrier, it was evident from CLSM images that intracellular delivery of the therapeutic protein significantly depleted the RNA level. Thus, this work provides a promising platform for the delivery of therapeutic proteins and chemotherapeutic drugs for efficient cancer treatment.

PH-sensitive doxorubicin-loaded polymeric nanocomplex based on β-cyclodextrin for liver cancer-targeted therapy.

BackgroundDoxorubicin (DOX) is one of the most effective treatments for hepatocellular carcinoma (HCC), but is restricted by its poor pharmacokinetics. Herein, we exploited efficient targeted drug delivery systems and they have been found to be a worthy strategy for liver cancer therapy.Materials and methodsWe investigated polymeric nanoparticles which were synthesized based on host–guest interaction between β-cyclodextrin and benzimidazole. The properties of nanoparticles with regard to size/shape, encapsulation efficiency, and drug release were investigated using conventional experiments. Cell proliferation assay in vitro, cell uptake assay, and cell apoptosis analysis were used to investigate cytotoxicity, uptake, and mechanism of targeted supramolecular prodrug complexes (TSPCs)-based self-assemblies and supramolecular prodrug complexes (SPCs)-based self-assemblies.ResultsThe pH-sensitive lactobionic acid (LA)-modified pH-sensitive self-assemblies were synthesized successfully. The results of in vitro released assay showed that the accelerated released of DOX from TSPCs-based self-assemblies with the decrease of pH value. When TSPCs-based self-assemblies were taken up by HepG2 cells, they demonstrated a faster release rate under acidic conditions and proved to have higher cytotoxicity than in the presence of LA. A mechanistic study revealed that TSPCs-based self-assemblies inhibited liver cell proliferation by inducing cell apoptosis.ConclusionThe pH-sensitive nanocomplex, as liver-targeted nanoparticles, facilitated the efficacy of DOX in HepG2 cells, offering an appealing strategy for the treatment of HCC.

A Chromatin-Mimetic Nanomedicine for Therapeutic Tolerance Induction.

The undesirable immune response poses a life-threatening challenge to human health. It not only deteriorates the therapeutic performance of biologic drugs but also contributes to various diseases such as allergies and autoimmune diseases. Inspired by the role of chromatin in the maintenance of natural immune tolerance, here we report a DNA-protein polymeric nanocomplex that can mimic the tolerogenic function of chromatin and induce an immune tolerance to its protein cargos. We first proved that the chromatin-mimetic nanomedicine loaded with keyhole limpet hemocyanin (KLH), a highly immunogenic model protein, could elicit a durable antigen-specific immune tolerance to KLH lasting for at least five weeks in mice. Following the proof-of-concept study, we demonstrated that this nanomedicine could be applied to improve the safety and efficacy of a biologic drug, PEGylated uricase, by attenuating the relevant antibody (Ab) responses. Moreover, we also demonstrated that prophylactic treatments with this nanomedicine could tolerize the immune system with the allergen of ovalbumin (OVA) and thus inhibit the occurrence of airway inflammation in an OVA-induced allergic asthma murine model. Collectively, our work illustrates a nature-inspired concept of immune tolerance induction and establishes a useful tool to specifically suppress unwanted immune responses for therapeutic purposes.

Polymeric Nanocomplex Encapsulating Iron Oxide Nanoparticles in Constant Size for Controllable Magnetic Field Reactivity.

The magnetic properties of nanoparticles make them ideal for using in various applications, especially in biomedical applications. However, the magnetic force generated by a single nanoparticle is low. Herein, we describe the development of nanocomplexes (size of 100 nm) of many iron oxide nanoparticles (IONPs) encapsulated in poly(lactic- co-glycolic acid) (PLGA) using the simple method of emulsion solvent evaporation. The response of the IONP-encapsulated PLGA nanocomplexes (IPNs) to an external magnetic field could be controlled by modifying the amount of IONPs loaded into each nanocomplex. In a constant size of IPNs, larger loading numbers of IONPs resulted in more rapid responses to a magnetic field. In addition, nanocomplexes were coated with a silica layer to facilitate the addition of fluorescent dyes. This allowed visualization of the responses of the IPNs to an applied magnetic field corresponding to the IONP loading amount. We envision that these versatile, easy-to-fabricate IPNs with controllable magnetism will have important potential applications in diverse fields.

Ammonium Bisphosphonate Polymeric Magnetic Nanocomplexes for Platinum Anticancer Drug Delivery and Imaging with Potential Hyperthermia and Temperature-Dependent Drug Release

Novel magnetite-ammonium bisphosphonate graft ionic copolymer nanocomplexes (MGICs) have been developed for potential drug delivery, magnetic resonance imaging, and hyperthermia applications. The complexes displayed relatively uniform sizes with narrow size distributions upon self-assembly in aqueous media, and their sizes were stable under simulated physiological conditions for at least 7 days. The anticancer drugs, cisplatin and carboplatin, were loaded into the complexes, and sustained release of both drugs was observed. The transverse NMR relaxivities (r2s) of the complexes were 244 s−1 (mM Fe)−1 which is fast compared to either the commercial T2-weighted MRI agent Feridex IV® or our previously reported magnetite-block ionomer complexes. Phantom MRI images of the complexes demonstrated excellent negative contrast effects of such complexes. Thus, the bisphosphonate-bearing MGICs could be promising candidates for dual drug delivery and magnetic resonance imaging. Moreover, the bisphosphonate MGICs generate heat under an alternating magnetic field of 30 kA·m−1 at 206 kHz. The temperature of the MGIC dispersion in deionized water increased from 37 to 41°C after exposure to the magnetic field for 10 minutes, corresponding to a specific absorption rate of 77.0 W·g−1. This suggests their potential as hyperthermia treatment agents as well as the possibility of temperature-dependent drug release, making MGICs more versatile in potential drug delivery applications.

A multifunctional ternary Cu(II)-carboxylate coordination polymeric nanocomplex for cancer thermochemotherapy

Metal-based photothermal therapy has been widely used in the biomedicine field and includes gold nanoparticles, silver nanoparticles and copper sulfide nanoparticles. Furthermore, the coordination bonding-based metal nanocomplex is a new generation of photothermal agents for cancer therapy due to its high photothermal transduction efficiency, good biocompatibility, biodegradation and bioactivity. In this study, we designed a coordination bonding-based copper (Cu(II))-carboxylate ternary architecture, which consists of a conjugate dopamine-modified nontoxic hyaluronic acid, copper ions and citric acid. When the Cu(II) coordinated with the carboxyl groups, the splitting d orbitals energy gap of Cu(II) and the capability of electron transition were enhanced, which can increase the extinction ability in the near-infrared region for enhancing photothermal therapy. Moreover, the degradation of hyaluronic acid by hyaluronidase highly expressed in the tumor microenvironment led to the release of Cu-citric acid complexes, thus exhibiting an additional chemotherapeutic effect. The nanocomplexes possessed high-performance photothermal conversion, determined to be 21.3%. The solution could be easily heated to above 42 °C, which was sufficient to ablate the cancer cells. An obvious decrease in cell viability was observed in B16F10 cells incubated with the nanocomplexes under laser at the lower concentration of 20 μg/mL Cu(II). Upon near-infrared laser irradiation, the nanocomplexes showed high photothermal therapy and chemotherapeutic efficacy for breast cancer in vivo. This study demonstrated that the Cu(II)-carboxylate coordination nanocomplex is a promising new effective and facilely prepared thermochemotherapy agent for combination therapy against cancer.