Tumor-targeted Chemotherapy Research Articles

Phase-separating Pt(IV)-graft-glycopeptides sequentially sensing pH and redox for deep tumor penetration and targeting chemotherapy.

Active-targeting nanomedicines have been widely employed in cancer treatment for increasing therapeutic index. However, the limited permeability caused by the binding site barrier (BSB) and size hindrances compromises their clinical antitumor efficacy in patients. Herein, learning from the liquid-liquid phase separation (LLPS) of bio-macromolecules, we report phase-separating glycopeptides (HEP) from polyhistidine (PHis) grafted hyaluronic acid (HA), which can sense the tumor extracellular pH and concomitantly overcome size and BSB dilemmas for enhanced tumor penetration. HEP aggregates into nanodroplets in solution at neutral pH. Upon reaching the acidic extracellular environment of tumors, the pH-responsive PHis triggers a phase separation, converting the coacervate nanodroplets into monomeric glycopeptides. This enables HEP conjugated with the platinum prodrug (HEPPt) to deeply penetrate into tumors by overcoming the BSB effect arising from the interaction between nanodroplets and cluster of differentiation 44 (CD44), as well as resolving the size challenges. Moreover, HEPPt in monomeric states exhibits promoted cellular uptake after pH-triggered phase separation, attributed to the transmembrane effect of exposed PHis. Subsequently, the rapid release of Pt(II), triggered by tumor intracellular reducing environment, exerts excellent antitumor activity. The phase-separating glycopeptides represent a promising platform for improving tumor penetration and intracellular delivery of therapeutic agents.

Novel metal-organic framework coated with chitosan-κ-carrageenan as a platform for curcumin delivery to cancer cells.

Metal-organic frameworks (MOFs) have shown great promise as pH-responsive drug delivery systems, with considerable potential for targeted cancer therapy. In this study, we synthesized a novel curcumin-loaded MOF, named UWO-2 (CUR@UWO-2), and developed its biocomposite form, CS-κ-Cr/CUR@UWO-2, by coating it with chitosan (CS) and κ-carrageenan (κ-Cr). Structural analysis through powder X-ray diffraction (PXRD) confirmed the successful synthesis of UWO-2 and the incorporation of CUR within the MOF structure. X-ray photoelectron spectroscopy (XPS) analysis revealed two distinct peaks at approximately 1021.15 eV and 1044.23 eV, corresponding to the Zn 2p₃/₂ and Zn 2p₁/₂ states, respectively. These peaks confirm the presence of the expected Zn2+ oxidation state in UWO-2, further validating its successful synthesis. Brunauer-Emmett-Teller (BET) analysis demonstrated a significant decrease in surface area (367.4 m2/g) and pore volume (0.296 cm3/g), validating the entrapment of CUR within the UWO-2 MOF structure. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images revealed that UWO-2 particles are spherical with a smooth surface, while CUR@UWO-2 exhibited a larger particle size, indicating successful curcumin loading. Thermogravimetric analysis (TGA) indicated enhanced thermal stability due to CUR loading, while swelling experiments revealed increased water absorption at neutral pH, supporting effective drug release under physiological conditions. Biodegradation studies showed sustained degradation of CUR@UWO-2 in the presence of lysozyme, confirming its suitability for in vivo applications. The drug delivery system achieved 21.9 % drug loading and 75.1 % encapsulation efficiency. Drug release experiments indicated accelerated release under acidic conditions, with the Korsmeyer-Peppas model identifying Fickian diffusion as the primary release mechanism. Cytotoxicity assessments showed increased cell death with CUR@UWO-2, enhanced by the synergistic effect of UWO-2, while the CS-κ-Cr coating enabled controlled, prolonged curcumin release. Confocal microscopy confirmed cellular uptake of CUR, underscoring the potential of the biocomposite for tumor-targeted chemotherapy applications in cancer treatment. This study highlights the potential of CUR@UWO-2, especially in its biocomposite form, for tumor-targeted drug delivery applications.

Hybrid prodrug nanoassembly for hypoxia-triggered immunogenic chemotherapy and immune modulation.

Tumor hypoxia is a critical driver of cancer progression, metastasis, and therapy resistance, posing significant challenges in effective cancer treatment. Hypoxia-activable prodrugs offer a promising strategy to target tumors in low-oxygen conditions, but their efficacy is often hindered by intrinsic properties and extrinsic cues. In this study, we developed a dual-prodrug nanoassembly system (CPPA) composed of a hypoxia-triggerable camptothecin (CPT)-based dimeric prodrug (CP) and a lipid-conjugated STAT3 antisense oligonucleotide (ASO) prodrug (PA), aiming to enhance tumor-targeted chemotherapy and overcome the immune evasion within the tumor microenvironment. The CPPA self-assemble into stable nanomicelle capable of co-delivering both agents directly to the tumor site, where the hypoxia-triggered release of CPT induces immunogenic cell death (ICD) while STAT3 inhibition enhances immune response. In murine breast cancer models, CPPA demonstrated superior therapeutic efficacy by improving tumor cell killing, promoting immune cell infiltration, and modulating the immunosuppressive tumor microenvironment. This combination therapy not only reversed drug resistance but also prevented the formation of the pre-metastatic niche, significantly inhibiting tumor progression and metastasis. These findings highlight the potential of CPPA as an effective strategy for enhancing cancer immunotherapy, offering a promising approach to address the complex challenges of tumor hypoxia, immune evasion, and resistance to chemotherapy.

Genetically Engineered Bacteria as A Living Bioreactor for Monitoring and Elevating Hypoxia-Activated Prodrug Tumor Therapy.

Tirapazamine (TPZ), an antitumor prodrug, can be activated in hypoxic environment. It specifically targets the hypoxic microenvironment of tumors and produces toxic free radicals. However, due to the tumor is not completely hypoxic, TPZ often fails to effectively treat the entire tumor tissue, resulting in suboptimal therapeutic outcomes. Herein, a low pathogenic Escherichia coli TOP10 is utilized to selectively colonize tumor tissues, disrupt blood vessels, and induce thrombus formation, leading to the expansion of hypoxic region and improving the therapeutic effect of TPZ. Additionally, a thermosensitive hydrogel is constructed by Pluronic F-127 (F127), which undergoes gelation in situ at the tumor site, resulting in sustained release of TPZ. To monitor the therapeutic process, it is genetically modified TOP10 by integrating the bioluminescent system luxCDABE (TOP10-Lux). The bioluminescent signal is associated with tumor hypoxia enhancement and thrombus formation, which is beneficial for therapeutic monitoring with bioluminescence imaging. In the murine colon cancer model, the TOP10-Lux combined with TPZ-loaded F127 hydrogel effectively suppressed tumor growth, and the treatment process is efficiently monitored. Together, this work employs genetically modified TOP10-Lux to enhance the therapeutic efficacy of TPZ and monitor the treatment process, providing an effective strategy for bacteria-based tumor-targeted chemotherapy and treatment monitoring.

Recurrent pancreatic cancer treated with N-803 and PD-L1 t-haNK followed by an EGFR-targeted nanocell drug conjugate.

Multimodal temporal therapy orchestrated to leverage immunotherapy, tumor-targeted chemotherapy, and natural killer (NK) cell therapy may provide an opportunity to induce immunogenic cell death for tumor response and increased survival in patients with recurrent cancer. The interleukin-15 (IL-15) superagonist N-803, an enhancer of NK cells, CD4 + T cells, cytotoxic CD8 + T cells, and memory T-cell activity, combined with off-the-shelf PD-L1-targeted high-affinity NK (PD-L1 t-haNK) cells represent novel immunotherapies designed to overcome an immunosuppressive tumor microenvironment (TME). The epidermal growth factor receptor-targeted antibody-nanocell conjugate E-EDV-D682 provides tumor-targeted chemotherapy in the form of its anthracycline metabolite PNU159682 (nemorubicin) cargo and is currently being studied in combination with immunomodulatory EDVs delivering the adjuvant α-galactosyl ceramide (GC). Here, we report the compassionate use treatment of this combination in a patient with recurrent, metastatic pancreatic cancer (mPC) after 3 lines of therapy. Under the initial single-patient Investigational New Drug (spIND) protocol, the patient received N-803, PD-L1 t-haNK cells, and the albumin doxorubicin conjugate aldoxorubicin for ~27 months. The patient's disease became stable on this regimen, and a transient complete response was observed by ~14 months of therapy. Due to progression, a second spIND protocol was designed whereby the patient received E-EDV-D682 plus EDV-GC for more than 24 months, which resulted in stable disease and the patient's continued survival at the time this report was written. The patient's extended survival despite the dire prognosis associated with recurrent mPC points to the merits of this temporal combination regimen in overcoming immuno-chemo resistance with enhanced immune activity required for tumor response and extended survival.

Multi-functional biotinylated platinum(IV)-SAHA conjugate for tumor-targeted chemotherapy.

The development of multi-functional Pt(IV) complexes as chemotherapeutic agents has gained growing attention in medical oncology. However, the design of multi-functional tumor-targeted Pt(IV) complexes with high hydrolytic stability remains challenging. Herein, we have developed a Pt(IV) prodrug conjugated with vorinostat as a multi-functional cancer therapeutic. In this design, the octahedral Pt(IV) prodrug of a DNA damaging anticancer drug cisplatin is tethered to the cancer cell targeting biotin ligand through one of the axial sites and the other axial site of the Pt(IV) center is attached to the anticancer drug vorinostat (also known as SAHA), a histone deacetylase inhibitor (HDACi) approved by the Food and Drug Administration (FDA) for treatment of cutaneous T-cell lymphoma. The designed biotinylated Pt(iv)-SAHA (Biotin-Pt(iv)-SAHA) conjugate is hydrolytically stable but reduced to Pt(II) species under intracellularly relevant conditions and concomitantly releases cisplatin and two of its axial ligands such as SAHA and biotin. The anticancer activity of the conjugate is investigated against a panel of cisplatin-sensitive human cancer cells, including cisplatin-resistant cells. Interestingly, the conjugate exhibited significantly higher cytotoxicity than the clinically approved anticancer drug cisplatin and slightly more cytotoxicity than the HDACi SAHA in all the tested cell lines. By combining the Pt(IV) prodrug of cisplatin with SAHA in the conjugate, synergistic cytotoxicity is achieved. The imaging studies revealed that the conjugate is taken up by cancer cells and shows dose-dependent cell death. The studies on our designed multi-pronged conjugate can be further optimized to enhance its efficacy, paving the way for developing a new class of clinically relevant chemotherapeutic agents.

Engineering Self-Assembled Nanomedicines Composed of Clinically Approved Medicines for Enhanced Tumor Nanotherapy.

The traditional nanocarriers are typically constructed to deliver anticancer agents for improving drug bioavailability and enhancing chemotherapeutic efficacy, but this strategy suffers from the critical issue of nanocarrier biosafety that hinders further clinical translation. In this work, a unique nanomedicine (PTX@ICG) has been rationally constructed by combining two clinically approved agents, i.e., paclitaxel (PTX) and indocyanine green (ICG), by a facile ultrasound-assisted self-assembly methodology. The formation of the nanostructure can effectively increase the enrichment of PTX and ICG molecules in the tumor site, and improve the utilization factor of hydrophobic PTX. Moreover, since the molecule interaction in PTX@ICG is mainly Van der Waals forces, the self-assembled structure can be spontaneously dissociated under laser irradiation and release PTX in situ to achieve safe tumor-targeted chemotherapy. Simultaneously, the released ICG can act as photothermic agents for photothermal therapy (PTT), thus combining chemotherapy and PTT to obtain an enhanced tumor nanotherapy via facile self-assembly. The synergistic chemo/photothermal tumor nanotherapy achieved the efficient tumor cell-killing effect and tumor-ablation ability, as systematically demonstrated both in vitro and in vivo. This work provides a distinct paradigm of the self-assembled nanomedicine design for effectively improving the drug bioavailability to achieve high antitumor efficacy.

Enhanced delivery of lenvatinib by hyaluronic acid-polyglycerol-stearate self-assembled micelles to inhibit hepatocellular carcinoma in vitro

CD44 protein is a well-known surface marker frequently observed in hepatocellular carcinoma (HCC) cells and plays crucial roles in the metastasis and invasion of the tumor. Hyaluronic acid (HA), an endogenous ligand, has the inherent ability to target and endocytosis into tumor cells via CD44 receptor-mediated internalization. The objective of this research was firstly to synthesize a hyaluronic acid-polyglycerol-stearate conjugate (HA-PG10-C18), which was then used to self-assemble lenvatinib (Len)-loaded micelles (HA@Len-M) for improved delivery of Len to HCC. The micelles were developed applying a lyophilization-hydration approach. The physicochemical characteristics, including zeta potential, particle size distribution, encapsulation efficiency, morphology, stability and in vitro release were thoroughly assessed for the micelles. Additionally, in vitro cellular uptake studies demonstrated that HA@Len-M facilitated improved uptake of micelles in H22 tumor cells. Furthermore, an in vitro proliferation study of H22 cells showed that the cytotoxicity of HA@Len-M was stronger than other preparations, likely because of the highly efficient delivery to H22 cells by HA@Len-M. These findings suggest that HA@Len-M may offer a CD44 receptor-mediated drug delivery system for eradicating H22, thus representing a potential strategy for tumor-targeted chemotherapy procedures.

Targeting Replication Stress and Chemotherapy Resistance with a Combination of Sacituzumab Govitecan and Berzosertib: A Phase I Clinical Trial.

Despite promising preclinical studies, toxicities have precluded combinations of chemotherapy and DNA damage response (DDR) inhibitors. We hypothesized that tumor-targeted chemotherapy delivery might enable clinical translation of such combinations. In a phase I trial, we combined sacituzumab govitecan, antibody-drug conjugate (ADC) that delivers topoisomerase-1 inhibitor SN-38 to tumors expressing Trop-2, with ataxia telangiectasia and Rad3-related (ATR) inhibitor berzosertib. Twelve patients were enrolled across three dose levels. Treatment was well tolerated, with improved safety over conventional chemotherapy-based combinations, allowing escalation to the highest dose. No dose-limiting toxicities or clinically relevant ≥grade 4 adverse events occurred. Tumor regressions were observed in 2 patients with neuroendocrine prostate cancer, and a patient with small cell lung cancer transformed from EGFR-mutant non-small cell lung cancer. ADC-based delivery of cytotoxic payloads represents a new paradigm to increase efficacy of DDR inhibitors. See related commentary by Berg and Choudhury, p. 3557.

Erythrocyte membrane-camouflaged DNA-functionalized upconversion nanoparticles for tumor-targeted chemotherapy and immunotherapy.

A synergistic combination of treatment with immunogenic cell death (ICD) inducers and immunoadjuvants may be a practical way to boost the anticancer response and successfully induce an immune response. The use of HR@UCNPs/CpG-Apt/DOX, new biomimetic drug delivery nanoparticles generated to combat breast cancer, is reported here as a unique strategy to produce immunogenicity and boost cancer immunotherapy. HR@UCNPs/CpG-Apt/DOX (HR-UCAD) consists of two parts. The core is composed of an immunoadjuvant CpG (a toll-like receptor 9 agonist) fused with a dendritic cell-specific aptamer sequence (CpG-Apt) to decorate upconversion nanoparticles (UCNPs) with the successful intercalation of doxorubicin (DOX) into the consecutive base pairs of Apt-CpG to construct an immune nanodrug UCNPs@CpG-Apt/DOX. The targeting molecule hyaluronic acid (HA) was inserted into a red blood cell membrane (RBCm) to form the shell (HR). HR-UCAD possessed a strong capacity to specifically induce ICD. Following DOX-induced ICD of cancer cells, sufficient exposure to tumor antigens and UCNPs@CpG-Apt (UCA) activated the tumor-specific immune response and reversed the immunosuppressive tumor microenvironment. In addition, HR-UCAD has good biocompatibility and increases the active tumor-targeting effect. Furthermore, HR-UCAD exhibits excellent near-infrared upconversion luminescence emission at 804 nm under irradiation with a 980 nm laser, which has great potential in biomedical imaging. Thus, the RBCm-camouflaged drug delivery system is a promising targeted chemotherapy and immunotherapy nanocomplex that could be used for effective targeted breast cancer treatment.

Novel biomimetic mesoporous silica nanoparticle system possessing targetability and immune synergy facilitates effective solid tumor immuno-chemotherapy

New strategies that enhance both the targetability of chemotherapy drugs and the synergistic effects of chemotherapy and immunotherapy are urgently needed for efficacious solid tumor therapy. In this study, a novel biomimetic nanoparticle system possessing the properties of tumor targeting and immune synergy was designed to meet these requirements. Mesoporous silica nanoparticles loaded with the chemotherapeutic drug doxorubicin (DOX) were coated with cell membranes modified by glycosylphosphatidylinositol (GPI)-anchored anti-HER2 single chain variable fragment (scFv) and the GPI-anchored co-stimulatory molecule CD80 (to promote solid tumor-targeted chemotherapy and cooperated immunotherapy, respectively). The impact of the nanotherapeutic system on both tumor-targeted chemotherapy and cellular immune response was investigated through in vitro and in vivo experiments. The results show that the novel biomimetic therapeutic system effectively promoted antitumor efficiency in vitro and in vivo. In addition, this therapeutic system further enhanced antitumor capacity by increasing CD8+ T cell activation and cytokine production and reducing myeloid-derived suppressor cell (MDSC) levels in tumors.

Lactobionic Acid-Navigated Gold Nanorods With Light-Triggered “on-Demand” Drug Release for Synergistic Photothermal-Chemotherapy

The rational design of the nanocarriers with active tumor targeting and specific chemotherapy for heat shock protein 90 (Hsp90) inhibition is attractive for combined chemo-photothermal therapy (PTT). Herein, a smart gold nanorod (GNR)-cored micelle (T-GNRAAG) was developed to encapsulate 17-allylamino-17-demethoxygeldanamycin (17-AAG, Hsp90 inhibitor) through a facile preparation approach. The characteristics of T-GNRAAG were evaluated both in vitro and in vivo. The designed nanoplatform possessed sufficient 17-AAG loading content and lactobionic acid-mediated active targeting for hepatoma cells. More importantly, the 808 nm laser irradiation not only initiated PTT for cell killing but also remotely triggered 17-AAG liberation within cancer cells via inducing the phase transition of poly(ɛ-caprolactone). All these features forcefully supported the effectiveness of T-GNRAAG in tumor growth inhibition. This work represents a proof-of-concept combinatorial chemo-PTT treatment.

Abstract LBA048: Lymph node metastasis targeted intranodal delivery of docetaxel improves treatment outcome

Abstract Despite recent advances in diagnostic modalities and cancer treatment guidelines, systemic chemotherapy for the lymph node (LN) metastasis has poor treatment efficacy using conventional drugs. Therefore, a novel method, lymphatic drug delivery system (LDDS), has been proposed in a pre-clinical experiment that directly injects the anticancer drug into sentinel LNs to deliver into their downstream LNs, aiming to inhibit tumor cell growth in those LNs. The injection duration of chemotherapy drugs using the LDDS will be less than the intratumoral or intralesion methods used in the clinic, and systemic toxicity will be less than tumor-targeted therapy or systemic chemotherapy. Our previous results indicated that the treatment efficacy increased in LDDS treated groups than systemic delivery. Here, we show the improvement of treatment efficacy by increasing osmotic pressure and viscosity of the drug solvent delivered by LDDS using the metastatic LN mouse model. First, a metastatic LN mouse model was created by inoculating luciferase-expressing tumor cells into subiliac LN (SiLN) of MXH10/Mo/lpr mouse to induce metastasis into the proper axillary LN (PALN). Next, 10 mg/kg docetaxel (DTX) with increased osmotic pressure and viscosity were injected into tumor-inoculated SiLN with an injection rate of 2400 μL/min on day 7 post-inoculation to inhibit tumor cell growth in the inoculation and metastatic site. Luciferase activity decreases in PALNs and SiLNs were observed in groups between 1140 kPa, 1960 kPa, and 2780 kPa (4, 11, and 38 mPa·s) groups without inducing any side effects. By histology, no tumor cells were confirmed in those LNs of the 1960 kPa group. Then, DTX at 1960 kPa, 11 mPa·s was injected into tumor-inoculated SiLN on day 21 post-inoculation with different injection speeds and volumes. We found that DTX at 1960 kPa, 11 mPa·s injected at the injection rate of 200 μL/min with 400 μL volume, can inhibit tumor cell growth in the PALN and delay tumor growth SiLN. Furthermore, the antitumor effects depended on the tumor progression stage in the LNs, and the injection rates and volumes of administered drugs. We anticipate these optimal ranges as a starting point for developing more effective drug regimens to treat metastatic LNs with the LDDS. Moreover, administrable drugs in this novel method of ultrasound-guided LDDS or LDDS at intra-operative or image-guided surgery are not limited only to anticancer agents. Citation Format: Ariunbuyan Sukhbaatar, Shouta Sora, Mori Shiro, Tetsuya Kodama. Lymph node metastasis targeted intranodal delivery of docetaxel improves treatment outcome [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr LBA048.

Recent advances in tumor-targeting chemotherapy drugs.

Recent advances in tumor-targeting chemotherapy drugs.

Chondroitin sulfate modified and adriamycin preloaded hybrid nanoparticles for tumor-targeted chemotherapy of lung cancer.

Promising cancer treatment requires the assistant of drug delivery systems (DDS) with the aim to increase the accumulation of drugs in tumor tissue. Herein, a hybrid DDS was successfully developed to integrate chondroitin sulfate (CS) and calcium carbonate (CC) in to one system. Anticancer drug adriamycin (Adr) was preloaded into CC nanoparticles to obtain Adr-loaded CC nanoparticles (CC/Adr). The resulted CS-CC/Adr nanoparticles as a biocompatible DDS was able to specifically target cancer cells to enhance the chemotherapy of lung cancer due to the surface modification of CS. Intracellular uptake as well as in vivo imaging results revealed the obtained CS-CC/Adr nanoparticles (size of ~100 nm) showed CS mediated tumor specific accumulation into A549 and LLC cells than unmodified CC/Adr, in which the CD44 receptor might be involved, which finally resulted in stronger anticancer capability than Adr or CC/Adr. As a result, CS-CC/Adr nanoparticles could be further extended to clinical administration in our future works.

A ROS-Responsive Self-Assembly Driven by Multiple Intermolecular Interaction Enhances Tumor-Targeted Chemotherapy.

To develop a drug carrier sensitive to reactive oxygen species (ROS), a nanocomplex (NCs) based on sulfuric hyaluronic acid (sHA)-anthocyanin (ATC) was developed. Doxorubicin (DOX) is loaded into the sHA-ATC NCs (AD@sHA) through intermolecular π-π stacking and hydrophobic interactions. AD@sHA can be prepared in aqueous phase by simple mixing method. In AD@sHA, DOX content and load efficiency are high. Compared with D@sHA (without ATC), the ROS-ATC co-mediated responsive degradation and drug release of AD@sHA was confirmed. In addition, AD@sHA also improved apoptosis of CD44+ colon cancer HT29cells. HT29 tumor-bearing mice model was used to confirm the role of AD@SHA in targeted tumor therapy. The results showed that AD@SHA could optimize the biodistribution of DOX. These data, from tumor volume and TUNEL analysis, observed the delay of tumor growth and apoptosis of cancer cells. Even more exciting is that AD@sHA significantly reduces the myelosuppression of DOX. This study means that AD@sHA has a better effect on chemotherapy for CD44-positive tumors.

Doxorubicin-loaded hollow gold nanospheres for dual photothermal ablation and chemoembolization therapy

BackgroundDoxorubicin-loaded hollow gold nanospheres (Dox@HAuNS) are a promising technology for simultaneous trans-arterial tumor-targeted chemotherapy delivery and thermal ablation. We evaluated the efficacy of intra-arterial delivery of Dox@HAuNS followed by photothermal ablation (PTA) in a rabbit model of liver cancer. Adult New Zealand white rabbits (N = 25) were inoculated with VX2 tumors into the left lobe of the liver. The animals were then randomized to sham surgery (N = 5), PTA only (N = 3), Dox@HAuNS only (N = 5), HAuNS + PTA (N = 5), and Dox@HAuNS + PTA (N = 7). Nanoparticles were delivered as an emulsion with Lipiodol (Guerbet, France) via a trans-arterial approach. Following nanoparticle delivery, PTA was performed using an 808-nm fibered laser at 1.5 W for 3 min. Thermography during PTA demonstrated a sustained elevation in tumoral temperature in both HAuNS + laser and Dox@HAuNS + laser treatment groups relative to animals that underwent laser treatment without prior nanoparticle delivery.ResultsThere was a significant decrease in tumor volumes in all three treatment arms relative to control arms (P = 0.004). Concentrations of intratumoral doxorubicin were significantly greater in animals treated with laser compared to those that were not treated with laser (P < 0.01).ConclusionsDoxorubicin-loaded HAuNS is a promising therapeutic agent for dual ablation/chemoembolization treatment of liver cancer.

Theranostic applications of smart nanomedicines for tumor-targeted chemotherapy: a review

Cancer is the result of disturbed cell functions. Cancer is induced by the accumulation of many genetic and epigenetic changes within the cell, expressed in the accumulation of chromosomal or molecular aberrations, which then leads to genetic instability. Chemotherapy is a major option to treat cancer, yet classical treatments induce toxic effects. Alternatively, cancer nanomedicines with tumor-targeted properties are very promising for improved safety and efficacy. Nanomedicines are sub-micrometer formulations designed to improve the biodistribution of anticancer drugs, resulting in modified toxicity, less off-target localization, enhanced efficacy and improved accumulation at the target site. For designing a targeted nanodrug system, the pathophysiological characteristics of tumors should be studied. This article explains how to make smart nanomedicines based on tumor-associated pathological features. Advantages include selective cell uptake, better drug release, increased therapeutic efficiency, receptor-mediated cell endocytosis, enhanced permeability and retention, and reduced systemic effects.

Gelated Vorinostat with inner-lysosome triggered release for tumor-targeting chemotherapy

Histonedeacetylase inhibitor (HDACi) has great potential in targeted antitumor therapy by inhibiting tumor migration, invasion, and metastasis. As one of the typical HDACis, vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) was approved as a therapeutic agent for cancer therapy, however, challenges remain due to their poor solubility, short half-life and low efficiency in cellular penetration. Considering the disadvantages of usual drug carriers, folate and vorinostat bound BSA nanogel (FVBN)was fabricated to implement higher solubility, stability, cellular uptake, and lipase-responsive release. With good dispersion and stability, FVBN significantly increased the cellular uptake of vorinostat through folate-mediated endocytosis. FVBN exhibited comparable cytotoxicity with free SAHA, and the growth of tumor cells was blocked in G1/G0 phase just like SAHA performed in cell cycle arrest tests. Moreover, FVBN not only effectively inhibited the growth of melanoma but also observably prevented pulmonary metastasis of melanoma. In the experiment against nude mice bearing solid ovarian cancer, FVBN showed excellent antitumor effect without liver damage, demonstrating the superiority of gelated and inner-lysosome triggered release strategies to the free SAHA, and it is promising to expand the scope of application of HDACi in clinical cancer therapy.

Polyampholyte-grafted single walled carbon nanotubes prepared via a green process for anticancer drug delivery application

We report a novel process for surface modified single-walled carbon nanotubes (SWCNTs) as drug nanocarriers by using facile and green synthetic methods. Firstly, polyampholytic alternating polymers having furfuryl amine and 3-(dimethylamino)-1-propylamine as functional groups were prepared via one-pot thiol-ene chemistry in sustainable conditions. The obtained polymers were then used to a direct functionalization onto the surface of SWCNTs through Diels-Alder click reaction conducted in aqueous media under ultrasonication. The resulting hybrid was characterized by 1H NMR, FT-IR, TGA and UV–vis measurements. The hybrid improved the drug loading content up to 150 wt%, indicating that they are potential doxorubicin (DOX) delivery nano-vehicles. Furthermore, the in-vitro drug release profiles showed that there was a burst release of DOX at pH 5.5 under an acidic condition in microenvironment of tumor cells, in contrast with a lower release rate at pH 7.4 in the physiological condition. Cell viability assays demonstrated the low cytotoxicity against the normal HEK293 cell of SWCNT hybrids, while they exhibited a high cytotoxic activity towards HeLa cancer cells. These evidences revealed the promising SWCNT-based drug carrier for tumor-targeting chemotherapy release in the cancer therapy.