Release Of Anticancer Drugs Research Articles

Multifunctional Protein-Decorated Bioactive Glass Nanoparticles for Tumor-Specific Therapy and Bioimaging In Vitro and In Vivo.

Multifunctional nanocarriers with a simple structure and biocompatibility for bioimaging, potential tumor targeting, and precise antitumor ability are promising in cancer therapy. Bioactive glass is an important biomaterial and has been used in clinical bone tissue repair due to the high biocompatibility and bioactivity. Herein, we report fetal bovine serum (FBS)-decorated europium-doped bioactive glass nanoparticles (EuBGN@FBS) with excellent biosafety and enhanced tumor targeting for cancer imaging and therapy. EuBGN@FBS showed the controlled photoluminescent properties and pH-responsive anticancer drug release behavior. The FBS decoration significantly enhanced the dispersibility in physiological medium and improved hemocompatibility and cellular uptake of EuBGN. Relative to EuBGN, EuBGN@FBS could also efficiently image the cancer cell and show significantly enhanced targeted tumor imaging and chemotherapy in vivo while retaining negligible side effects. The simple and biocompatible structure with efficient tumor targeting, imaging, and therapy makes EuBGN@FBS highly promising in future cancer therapy.

Computational Study on the Mechanism of the Photouncaging Reaction of Vemurafenib: Toward an Enhanced Photoprotection Approach for Photosensitive Drugs.

The photochemical behavior of the photosensitive first-line anticancer drug vemurafenib (VFB) is of great interest due to the impact of such behavior on its pharmacological activity. In this work, we computationally elucidated the mechanism of the photoinduced release of VFB from the 4,5-dimethoxy-2-nitrobenzene (DMNB) photoprotecting group by employing various density functional theory (DFT)/time-dependent DFT (TD-DFT) approaches. The computational investigations included a comparative assessment of the influence of the position of the photoprotecting group as a substituent on the thermodynamics and kinetics of the photouncaging reactions of two VFB-DMNB prodrugs, namely pyrrole (NP) and sulfonamide (NS). With the aid of the DFT calculations concerning the activation energy barrier (∆G‡), the obtained results suggest that the step of the photoinduced intramolecular proton transfer of the DMNB moiety is not detrimental concerning the overall reaction profile of the photouncaging reaction of both prodrugs. However, the obtained results suggested that the position of the substitution position of the DMNB photoprotecting group within the prodrug structure has a substantial impact on the photouncaging reaction. In particular, the DMNB-Ns-VFB prodrug exhibited a notable increase in ∆G‡ for the key step of ring opining within the DMNB moiety indicative of potentially hindered kinetics of the photouncaging process compared with DMNB-Np-VFB. Such an increase in ∆G‡ may be attributed to the electronic influence of the NP fragment of the prodrug. The results reported herein elaborate on the mechanism of the photoinduced release of an important anticancer drug from photoprotecting groups with the aim of enhancing our understanding of the photochemical behavior of such photosensitive pharmaceutical materials at the molecular level.

Magnetic κ-carrageenan/chitosan/montmorillonite nanocomposite hydrogels with controlled sunitinib release

This work aimed to design montmorillonite-incorporated pH-responsive and magnetic κ-carrageenan/chitosan hydrogels via a completely green route for controlled release of sunitinib anticancer drug. This was accomplished by ionic cross-linking of two biopolymers, κ-carrageenan and chitosan, in the presence of magnetic montmorillonite (mMMt) nanoplatelets. Interestingly, it was observed that the amount of mMMt affected not only the microstructure of hydrogels, but also the drug loading efficiency of nanocomposite hydrogels was noticeably increased by introducing mMMt (from 69 to 96%). The in vitro sunitinib release experiments showed that a low content of loaded sunitinib was released from all hydrogels in the buffered solution with pH 7.4. In contrast, a relatively sustained release with a high content of drug release was observed in the acidic solution of pH 5.5. During 48 h, the hydrogels nanocomposite containing a high content of mMMt showed cumulative release of 64.0 and 8.6% at pH 5.5 and 7.4, respectively. During two days, while the cumulative release of sunitinib was obtained 84.3% for the magnetic-free hydrogel, the magnetic ones showed 74.4 and 64% with the low and high contents of magnetic MMt, respectively. The developed κ-carrageenan/chitosan hydrogels with a high capacity of drug loading and subsequent pH-sensitive drug release can be considered in prolonged cancer therapy with reduced side effects.

Biomineralization inspired synthesis of CaCO3-based DDS for pH-responsive release of anticancer drug

Calcium carbonate (CaCO3) is an ideal candidate for use in drug delivery system (DDS) for cancer cure due to good biocompatibility, pH-sensitivity and low-toxicity. However, developing a method that is fast and green, and have large-scale production of CaCO3-based DDS remains a challenge. Here, inspired by biomineralization, for the first time, we develop a one-pot, l-lysine (Lys)-mediated biomineralization method using a CO2 bubbling procedure to green, simply and quickly prepare CaCO3-based DDS. The presence of Lys not only improved the yield of CaCO3, but also controled morphology and crystal phase of CaCO3. Meanwhile, two different crystal forms of CaCO3 microspheres were used in the pH-responsive release of cancer drug Sanguinarine (SAN): calcite CaCO3 (CC) and vaterite CaCO3 (VC). The structure of the as-prepared CC and VC was characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and Brunauer-Emmett-Teller analysis (BET). The possible formation mechanism was proposed. As a potential DDS, both different DDS showed good drug-loading capacity (CC: 63.5 %; VC: 51.9 %), good biocompatibility, pH-sensitivity and low-toxicity. Meanwhile, after loading the SAN, it had obvious inhibitory effects to cancer cells. However, they presented significant differences in drug loading rate, loading capacity and pH-sensitivity due to differences in crystal form and morphology. This biomineralization method of green synthesis of CaCO3-based DDS using CO2 provided a possibility for industrial application of DDS, and the comparative study of CaCO3 with different morphologies and crystal forms gave a good idea for the design of DDS.

Tailoring nano-copolymer/CNTs composite and its application in drug delivery

This work aimed to overcome the main drawbacks of some essential anticancer drugs as 5-Fluorouracil (5-FU) by controlled loading with novel drug carriers. By a differential microemulsion technique, nanosized particles derived from a copolymer of poly(methyl methacrylate (MMA) and 2-hydroxyethyl methacrylate (HEMA)) with different monomer ratios have been synthesized and used as a drug carrier. Poly(MMA-co-HEMA)/MWCNT nanocomposite was also synthesized using an in-situ microemulsion polymerization technique and used as a 5-FU carrier. Different techniques have characterized these ground-breaking drug delivery systems such as FT-IR, XRD, TEM, TGA, zeta potential, and a particle size analyzer. The effects of monomer feed composition, 5-FU content, and MWCNTs content on morphological and structural properties, in-vitro 5-FU release, and entrapment efficiency (EE%) have been studied. It was noted that the inclusion of MWCNTs in the 5-FU-loaded polymer increases the thermal stability and raises the entrapment efficiency (EE%) to hit 99% at CNTs:5-FU ratio of 2:1. The anticancer drug release from the co-polymeric nanospheres depends on the HEMA ratio, 5-FU/copolymer ratio, CNT/5-FU ratio, and the pH of the medium. The optimized nanocomposite demonstrated higher anti-tumor activity against the cell lines CaCo-2, MCF-7, and HepG-2 and higher cytotoxicity against HepG-2 relative to CaCo-2 and MCF-7.

Light-Activated Local Drug Delivery From Hydrogels: Potential for GBM Treatment

Following post-operative treatment, the vast majority of GBMs recur, usually within 2 cm of the tumor resection margin. Since these tumors seldom metastasize outside the CNS, improved localized therapies should prove beneficial. Drug delivery systems (DDS) that allow control over drug release by an externally applied energy, such as light, have the potential of improving the results of chemotherapy. Light-activated hydrogel DDS, implanted in the operative cavity formed by tumor resection, bypasses the blood brain barrier and allows for a precise spatio-temporal control of drug release or drug activation. Localized, on-demand release of anticancer drugs to normal brain infiltrated by tumor cells should therefore improve therapeutic efficacy and minimize systemic, drug-related side effects. Various forms of light-activated hydrogels have utilized near infrared, visible or ultraviolet wavelength irradiation. One form of hydrogel, fibrin glue (FG), composed of a combination of fibrinogen and thrombin, has several characteristics that make it well-suited for this form of sustained release drug delivery. Unlike most synthetic hydrogels, FG is a natural product and has been used clinically in surgery for decades, so its biocompatibility and lack of toxicity has been clearly proven. The light-driven drug activation technology, photochemical internalization (PCI) has been shown to enhance the intracellular efficacy of chemotherapeutic agents released from fibrin glue. A summary of the light-activated hydrogel techniques developed for the site and temporal-specific delivery of chemotherapy for the treatment of GBM will be discussed in this review.

Novel cyclomatrix polyphosphazene nanospheres: preparation, characterization and dual anticancer drug release application

In this study, it is aimed to investigate in vitro pH-responsive, dual anticancer drug release from cyclomatrix polyphosphazene nanospheres for combination chemotherapy. For the first time, novel cyclomatrix polyphoshazene nanospheres that contain curcumin and quercetin were prepared by one-pot drug self-framed precipitation polymerization. Curcumin and quercetin were used both as monomers in synthesis of nanospheres and as released drugs. The nanospheres were characterized by SEM, EDX, FTIR, solid state 31P-NMR, BET, XRD, DLS and UV–vis techniques. It was determined that nanospheres contained 500 mg.g−1 drugs (DL%: 36% curcumin, 14% quercetin; EE%: 47.2% curcumin and 23% quercetin). The controlled release of drugs was investigated in lysosomal pH (pH:5.5) and blood pH (pH:7.4), at 37 °C, using dialysis membrane. Quercetin and curcumin were released from nanospheres at pH 7.4: 18.14%, 2.25%; pH 5.5: 10.12%, 1.02%, respectively, at 7 days. The release kinetic was determined to be Korsmeyer-Peppas kinetic model according to correlation coefficients, and the release mechanism was non-Fickian model for nanospheres.

Stimuli-Responsive Hydrogels for Cancer Treatment: The Role of pH, Light, Ionic Strength and Magnetic Field.

Simple SummaryCancer remains as the world second leading cause of death. The severe side effects associated to high doses of chemotherapy and the development of drug resistance are major drawbacks for a successful cancer treatment. Therefore, new formulations that promote localized therapy at tumor sites are needed to improve the therapeutic outcomes and patient welfare. The use of hydrogels is a very promising alternative, since they can be composed by smart materials able to respond to external factors, changing their properties accordingly and promoting a localized drug delivery. As a result, a more specific, efficient, and less toxic local cancer treatment can be accomplished. In this context, the most important characteristics of hydrogels recent studies regarding the application of pH-, light-, ionic strength-, and magnetic-responsive hydrogels in cancer treatment are here presented.Cancer remains as the second leading cause of death, worldwide. Despite the enormous important advances observed in the last decades, advanced stages of the disease remain incurable. The severe side effects associated to systemic high doses of chemotherapy and the development of drug resistance impairs a safe and efficiency anticancer therapy. Therefore, new formulations are continuously under research and development to improve anticancer drugs therapeutic index through localized delivery at tumor sites. Among a wide range of possibilities, hydrogels have recently gained special attention due to their potential to allow in situ sustained and controlled anticancer drug release. In particular, stimuli-responsive hydrogels which are able to change their physical state from liquid to gel accordingly to external factors such as temperature, pH, light, ionic strength, and magnetic field, among others. Some of these formulations presented promising results for the localized control and treatment of cancer. The present work aims to discuss the main properties and application of stimuli-responsive hydrogels in cancer treatment and summarize the most important advances observed in the last decades focusing on the use of pH-, light-, ionic strength-, and magnetic-responsive hydrogels.

Screening for new peptide substrates for the development of albumin binding anticancer pro-drugs that are cleaved by prostate-specific antigen (PSA) to improve the anti tumor efficacy

Several attempts have been made over the past decade to explore the concept of prodrug strategies that exploit PSA as a molecular target for the release of anticancer drugs in prostate tumors using various prostate specific antigen (PSA)-cleavable peptide linkers, but the desired antitumor and antimetastatic efficacy has not yet been fully achieved. We set out to look for new PSA-cleavable peptide substrates that could be cleaved more rapidly and efficiently than the previously used peptides. To look for the most susceptible PSA-cleavable peptide substrates, we used the so-called spot technology. With the following general formula, we designed 25 different fluorogenic heptapeptides; Cellulose-P5-P4-P3-P2-P1-P1′-P2’ (Fluorophore). The increase of the fluorescence in the supernatant of the reaction mixture was monitored using a 96-well fluorometric plate reader with excitation of λex 485 nm and λem 535 nm. Three sequences showed a high fluorogenic liberation after incubation with PSA, i.e., Arg-Arg-Leu-His-Tyr-Ser-Leu (7), Arg-Arg-Leu-Asn-Tyr-Ser-Leu (8) and Arg-Ser-Ser-Tyr-Arg-Ser-Leu (23). Future incorporation of these optimized substrates in the PSA-cleavable prodrug formulations could further optimize the cleavage pattern and so the release characteristics of these prodrugs to rapidly and efficiently liberate the free cytotoxic agents inside the tumor tissues.

A novel microwave stimulus remote-controlled anticancer drug release system based on Janus TiO2-x&mSiO2 nanocarriers

In this work, we used a simple method to construct Janus-shaped TiO2-x&mSiO2 nanoparticles composed of gray-black titanium dioxide (TiO2-x) and mesoporous silica (mSiO2) serving as carriers to improve the microwave-controlled release performance. In the composite materials, on one hand, the rod-shaped mSiO2 could realize high-efficiency drug loading, on the other hand, spherical TiO2-x featuring oxygen vacancy acted as the main microwave absorber. The overall spatial separation between titanium dioxide and silicon dioxide was crucial to enhance microwave conversion efficiency. The Janus-liked nanomaterial was made up of TiO2-x nanosphere with a diameter of approximately 180 nm on one end and rod-shaped mesoporous silica with about 220 nm in length and 100 nm in diameter on the other end, and the specific surface area of the entire material was 203.25 m2/g. Meanwhile, the cumulative doxorubicin hydrochloride (DOX) loading rate of the carrier reached up to 38 wt% after 24 h. The loading process of the DOX was exothermic, and the noncovalent interaction between the DOX and Janus TiO2-x&mSiO2 carrier was mainly van der Waals force. Furthermore, the rates of drug release at 24 h were up to 61 wt%, 69 wt% and 89 wt% at pH 7.0, 5.0 and 3.0, respectively. After microwave stimulation at pH 7.0, the rate of drug release increased observably from 61% to 88% compared to that of non-microwave irradiation. The order of the microwave thermal conversion capability of the samples was Janus TiO2-x&mSiO2 > Janus TiO2&mSiO2 > core-shell TiO2-x@mSiO2. Besides, cytotoxicity tests indicated that Janus TiO2-x&mSiO2 nanoparticles had good biocompatibility. Therefore, the multifunctional carrier of the Janus-shaped configuration could not only release drugs under pH control, but also be further triggered by microwave stimulation. The Janus-shaped TiO2-x&mSiO2 nanoparticles will look forward to laying foundation to the application in drug delivery systems.

AN ARTICLE REVIEW ON TUMOR-SPECIFIC AUTOMATED DRUG DELIVERY SYSTEM

In this article, targeted and controlled anticancer drug delivery and release with magneto-electric nanoparticles, published in 2016, rodzinski et al., explain how magneto-electric nanoparticles abbreviated as (mens) can be used to monitor the delivery of drugs and their release into cancer cells. They go further to explain how they use this automated drug delivery system to eradicate cancerous tumor cells.

CRISPR-dCas9-Guided and Telomerase-Responsive Nanosystem for Precise Anti-Cancer Drug Delivery.

Nanodrug delivery systems are very promising for highly efficient anticancer drug delivery. However, the present nanosystems are commonly located in the cytoplasm and mediate uncontrolled release of drugs into cytosol, while a large number of anticancer drugs function more efficiently inside the nucleus. Here, we constructed a CRISPR-dCas9-guided and telomerase-responsive nanosystem for nuclear targeting and smart release of anticancer drugs. CRISPR-dCas9 technology has been employed to achieve conjugation of mesoporous silica nanoparticles (MSNs) with a high payload of the active anticancer drug, doxorubicin (DOX). A specifically designed wrapping DNA was used as a telomerase-responsive biogate to encapsulate DOX within MSNs. The wrapping DNA is extended in the presence of telomerase, which is highly activated in tumor cells, but not in normal cells. The extended DNA sequence forms a rigid hairpin-like structure and diffuses away from the MSN surface. CRISPR-dCas9 specifically targets telomere-repetitive sequences at the tips of chromosomes, facilitating the precise delivery of the nanosystem to the nucleus, and effective drug release triggered by telomerase that was enriched around telomeric repeats. This study provides a strategy and nanosystem for nuclear-targeted delivery and tumor-specific release of anticancer drugs that will maximize the efficiency of cancer cell destruction.

Formulation of Quaternized Aminated Chitosan Nanoparticles for Efficient Encapsulation and Slow Release of Curcumin.

An effective drug nanocarrier was developed on the basis of a quaternized aminated chitosan (Q-AmCs) derivative for the efficient encapsulation and slow release of the curcumin (Cur)-drug. A simple ionic gelation method was conducted to formulate Q-AmCs nanoparticles (NPs), using different ratios of sodium tripolyphosphate (TPP) as an ionic crosslinker. Various characterization tools were employed to investigate the structure, surface morphology, and thermal properties of the formulated nanoparticles. The formulated Q-AmCs NPs displayed a smaller particle size of 162 ± 9.10 nm, and higher surface positive charges, with a maximum potential of +48.3 mV, compared to native aminated chitosan (AmCs) NPs (231 ± 7.14 nm, +32.8 mV). The Cur-drug encapsulation efficiency was greatly improved and reached a maximum value of 94.4 ± 0.91%, compared to 75.0 ± 1.13% for AmCs NPs. Moreover, the in vitro Cur-release profile was investigated under the conditions of simulated gastric fluid [SGF; pH 1.2] and simulated colon fluid [SCF; pH 7.4]. For Q-AmCs NPs, the Cur-release rate was meaningfully decreased, and recorded a cumulative release value of 54.0% at pH 7.4, compared to 73.0% for AmCs NPs. The formulated nanoparticles exhibited acceptable biocompatibility and biodegradability. These findings emphasize that Q-AmCs NPs have an outstanding potential for the delivery and slow release of anticancer drugs.

Redox-sensitive polymeric micelles with aggregation-induced emission for bioimaging and delivery of anticancer drugs

BackgroundNano-drug delivery systems show considerable promise for effective cancer therapy. Polymeric micelles have attracted extensive attention as practical nanocarriers for target drug delivery and controlled drug delivery system, however, the distribution of micelles and the release of the drug are difficult to trace in cancer cells. Therefore, the construction of a redox-sensitive multifunctional drug delivery system for intelligent release of anticancer drugs and simultaneous diagnostic imaging and therapy remains an attractive research subject.ResultsTo construct a smart drug delivery system for simultaneous imaging and cancer chemotherapy, mPEG-ss-Tripp was prepared and self-assembled into redox-sensitive polymeric micelles with a diameter of 105 nm that were easily detected within cells using confocal laser scanning microscopy based on aggregation-induced emission. Doxorubicin-loaded micelles rapidly released the drug intracellularly when GSH reduced the disulfide bond. The drug-loaded micelles inhibited tumor xenografts in mice, while this efficacy was lower without the GSH-responsive disulfide bridge. These results establish an innovative multi-functional polymeric micelle for intracellular imaging and redox-triggered drug deliver to cancer cells.ConclusionsA novel redox-sensitive drug delivery system with AIE property was constructed for simultaneous cellular imaging and intelligent drug delivery and release. This smart drug delivery system opens up new possibilities for multifunctional drug delivery systems.

A novel multifunctional NCQDs-based injectable self-crosslinking and in situ forming hydrogel as an innovative stimuli responsive smart drug delivery system for cancer therapy

In this work, we offer an easy approach to develop a novel injectable, pH sensitive and in situ smart drug delivery system for use in cancer treatments. The developed hydrogels containing nitrogen doped carbon quantum dots (NCQD), doxorubicin (Dox) and hydroxyapatite (HA) were obtained by in situ self-crosslinking. Characterization of the synthesized nanomaterials, interactions between NCQD/Dox/HA hydrogel structure were carried out by TEM, FESEM, EDS, FTIR, XPS, XRD, Zeta potential, DLS, UV–Vis, SEM, gelation time, injectability and DIST measurements. In addition, antibacterial evaluation which was performed against Staphylococcus aureus realized that HA compound significantly increased the antibacterial activity of the hybrid hydrogel. The anticancer drug release to the tumor cell microenvironment with a pH of 5.5 was found to be higher compared to the release in the normal physiological range of pH 6.5 and 7.4. MTT and live/dead assays were also performed using L929 fibroblastic cell lines to investigate the cytotoxic behavior of NCQDs, and NCQDs/Dox/HA hydrogels. Furthermore, the NCQDs/Dox/HA hydrogel could transport Dox within a MCF-7 cancerous cell at specifically acidic pH. Additionally, imaging of cell line was observed using NCQDs and their use in imaging applications and multicolor features in the living cell system were evaluated. The overall study showed that in situ formed NCQDs/Dox/HA hydrogel represented a novel and multifunctional smart injectable controlled-release drug delivery system with great potential, which may be considered as an attractive minimal invasive smart material for future intelligent delivery of chemotherapeutic drug and disease therapy applications.

Composition and surface chemistry engineering of graphene grafting chitosan for stimuli-responsive cancer therapy: An in-silico study

Graphene-based drug delivery studies have been utilized in pharmaceutical science, primarily a molecular investigation of cancer therapy. The energetic interactions between drugs and graphene nanosheets are one of the critical components of cancer treatment studies. In the present work, Graphene-based nanosheets, including; carboxylated graphene (CGRA), Silicon-doped graphene (SiGRA) and Phosphorus-doped graphene (PGRA) were utilized as carriers for Doxorubicin/Paclitaxel co-delivery. Furthermore, these nanosheets were modified by pH- and thermal-sensitive co-polymer, named trimethyl chitosan (TMC)- b- N, N- dimethyl acrylamide (DMAA). TMC-DMAA co-polymer benefits from remarkable features leading to its pH- and temperature-sensitivity for drug loading and stimuli-responsive release purposes. First, the TMC-DMAA co-polymer, as well as functionalized graphene molecules, have been optimized at acidic and neutral conditions. Then, the loading and release of drugs in the normal and cancerous conditions were investigated by molecular dynamics tools, respectively. Finally, the validation test clarified the accuracy and precision of the simulation systems. The results indicated that TMC-DMAA functionalized graphene nanocarrier could retain drug molecules from unwanted interactions in normal tissues while causing the drug release in a pH and temperature-sensitive manner at the tumor microenvironment. Moreover, P-doped and Si-doped modification increased the capacity of drug loading on graphene nanosheets. By investigating molecular insight, shedding the light of anti-cancer drug loading and release achieved. The results of this study would help future studies about cancer drug delivery research. • DOX and PAX co-delivery by functionalized graphene nanocarriers studied by molecular dynamics simulation. • Van der Waals and electrostatic interactions and hydrogen bonds work throughout the combination. • Effect of dimethyl acrylamide -trimethyl chitosan on the drug release kinetics is obtained via molecular dynamics. • Drug release from the carboxylated graphene is controlled by the modifying polymer at various pH conditions. • P-doped and Si-doped graphene increased the capacity of loading at normal condition.

Tissue-adhesive and highly mechanical double-network hydrogel for cryopreservation and sustained release of anti-cancer drugs

Applications of hydrogels served as drug carriers are severely limited by several main drawbacks of instable network structure, weak mechanical strength, shortage of tissue-adhesive ability, as well as poor anti-frozen performance, especially for some anti-cancer drugs (e.g., lomustine) those should be stored at subzero temperature to maintain their bioactivity. In the present work, a kind of hybrid polyacrylamide/alginate-CaCl2 (PAAm/Alg-Ca) based double-network (DN) hydrogel presented high tensile strength of 61.81 ​± ​5.14 ​kPa, a low water contact angle of 22.5° ​± ​0.8°, and sufficient adhesion on various wet substrates (234.56 ​± ​8.55 ​Pa). More interestingly, pH-responsive swelling behavior, excellent cold-resistance, as well as efficient recoverability at a low temperature of −20 ​°C was shown in such hydrogel. On the basis of biocompatibility result and a sustained drug release behavior using lomustine as a testing model, our proposed PAAm/Alg-Ca based DN hydrogel paves the way for development of anti-cancer drugs cryopreservation and delivery vehicle.

Targeting self-assembled F127-peptide polymer with pH sensitivity for release of anticancer drugs.

The treatment of breast cancer mainly relies on chemotherapy drugs, which present significant side effects. The most typical example is the cardiotoxicity and bone marrow suppression associated with doxorubicin (DOX). Therefore, this drug is not the first choice in clinical treatment. We designed ATN-FFPFF-ATN, a new targeted antitumor drug carrier, polymerized from phenylalanine dipeptide (FF), ATN-161 peptide, and Pluronic® F-127. The peptide and Pluronic® F-127 are linked with acetal and are, therefore, acid-sensitive. As cancer can reduce pH through complex mechanisms and subsequently maintain acid ambience, our vehicle can smartly unravel at a peculiar position, through which the drug can specifically accumulate inside the tumor. ATN-161 is a protein ligand of integrin α5β1, which is highly expressed on the surface of some breast cancer cells. This targeting peptide sequence can play a role in the selective delivery of DOX to tumor cells. The DOX-carrying vector was able to significantly inhibit cell proliferation and promote cell apoptosis in MDA-MB-231 cells. Based on these results, ATN-FFPFF-ATN with pH response is a promising vehicle for DOX delivery.

Targeted delivery and stimulus-responsive release of anticancer drugs for efficient chemotherapy

Chemotherapy is currently an irreplaceable strategy for cancer treatment. Doxorubicin hydrochloride (DOX) is a clinical first-line drug for cancer chemotherapy. While its efficacy for cancer treatment is greatly compromised due to invalid enrichment or serious side effects. To increase the content of intracellular targets and boost the antitumor effect of DOX, a novel biotinylated hyaluronic acid-guided dual-functionalized CaCO3-based drug delivery system (DOX@BHNP) with target specificity and acid-triggered drug-releasing capability was synthesized. The ability of the drug delivery system on enriching DOX in mitochondria and nucleus, which further cause significant tumor inhibition, were investigated to provide a more comprehensive understanding of this CaCO3-based drug delivery system. After targeted endocytosis by tumor cells, DOX could release faster in the weakly acidic lysosome, and further enrich in mitochondria and nucleus, which cause mitochondrial destruction and nuclear DNA leakage, and result in cell cycle arrest and cell apoptosis. Virtually, an effective tumor inhibition was observed in vitro and in vivo. More importantly, the batch-to-batch variation of DOX loading level in the DOX@BHNP system is negligible, and no obvious histological changes in the main organs were observed, indicating the promising application of this functionalized drug delivery system in cancer treatment.

Single component photoresponsive fluorescent organic nanoparticles: a smart platform for improved biomedical and agrochemical applications.

In the last two decades, light responsive nano drug delivery systems (DDSs) have gained considerable importance, particularly in the area of biology and medicine. In general, light responsive nano DDSs are bicomponent and constructed using two ingredients, namely a nanocarrier and a phototrigger. The synthesis of these bicomponent nano DDSs requires multiple steps, which limits their applications. Hence, we have reported single component light responsive nano DDSs using fluorescent organic nanoparticles (FONPs) which acted both as a nanocarrier and a phototrigger. This feature article provides an overview of recently developed light responsive single component FONPs and their applications in the regulated release of anticancer drugs, gasotransmitters, antibacterial agents, and pesticides, and also as efficient PDT agents. We have summarised the synthesis, characterisation, and photophysical, photochemical, and in vitro behaviours of these light responsive FONPs. In addition, we also discussed the advantages of using FONPs as a nano DDS for cellular studies like: excellent biocompatibility, efficient cellular internalisation, real time monitoring of the drug release ability inside the cells, and enhanced cytotoxicity due to regulated release of bioactive molecules inside the cells.