Research Progress in the Field of Tumor Model Construction Using Bioprinting: A Review.

The development of therapeutic drugs and methods has been greatly facilitated by the emergence of tumor models. However, due to their inherent complexity, establishing a model that can fully replicate the tumor tissue situation remains extremely challenging. With the development of tissue engineering, the advancement of bioprinting technology has facilitated the upgrading of tumor models. This article focuses on the latest advancements in bioprinting, specifically highlighting the construction of 3D tumor models, and underscores the integration of these two technologies. Furthermore, it discusses the challenges and future directions of related techniques, while also emphasizing the effective recreation of the tumor microenvironment through the emergence of 3D tumor models that resemble in vitro organs, thereby accelerating the development of new anticancer therapies.

Acidity-Triggered Transformable Polypeptide Self-Assembly to Initiate Tumor-Specific Biomineralization.

Biomineralization is a normal physiological process that includes nucleation, crystal growth, phase transformation, and orientation evolution. Notably, artificially induced biomineralization in the tumor tissue has emerged as an unconventional yet promising modality for malignancy therapy. However, the modest ion-chelating capabilities of carboxyl-containing biomineralization initiators lead to a deficient blockade, thus compromising antitumor efficacy. Herein, a biomineralization-inducing nanoparticle (BINP) is developed for blockade therapy of osteosarcoma. BINP is composed of dodecylamine-poly((γ-dodecyl-l-glutamate)-co-(l-histidine))-block-poly(l-glutamate-graft-alendronate) and combines a cytomembrane-insertion moiety, a tumor-microenvironment (TME)-responsive component, and an ion-chelating motif. After intravenous injection into osteosarcoma-bearing mice, BINP responds to the acidic TME to expose the dodecyl group on the surface of the expanded nanoparticles, facilitating their cytomembrane insertion. Subsequently, the protruding bisphosphonic acid group triggers continuous ion deposition to construct a mineralized barrier around the tumor, which blocks substance exchange between the tumor and surrounding normal tissues. The BINP-mediated blockade therapy displays tumor inhibition rates of 59.3% and 52.1% for subcutaneous and orthotopic osteosarcomas, respectively, compared with the Control group. In addition, the suppression of osteoclasts by the alendronate moiety alleviates bone dissolution and further inhibits pulmonary metastases. Hence, the BINP-initiated selective biomineralization provides a promising alternative for clinical osteosarcoma therapy.

Smart nanogels for cancer treatment from the perspective of functional groups.

Introduction: Cancer remains a significant health challenge, with chemotherapy being a critical treatment modality. However, traditional chemotherapy faces limitations due to non-specificity and toxicity. Nanogels, as advanced drug carriers, offer potential for targeted and controlled drug release, improving therapeutic efficacy and reducing side effects. Methods: This review summarizes the latest developments in nanogel-based chemotherapy drug delivery systems, focusing on the role of functional groups in drug loading and the design of smart hydrogels with controlled release mechanisms. We discuss the preparation methods of various nanogels based on different functional groups and their application in cancer treatment. Results: Nanogels composed of natural and synthetic polymers, such as chitosan, alginate, and polyacrylic acid, have been developed for chemotherapy drug delivery. Functional groups like carboxyl, disulfide, and hydroxyl groups play crucial roles in drug encapsulation and release. Smart hydrogels have been engineered to respond to tumor microenvironmental cues, such as pH, redox potential, temperature, and external stimuli like light and ultrasound, enabling targeted drug release. Discussion: The use of functional groups in nanogel preparation allows for the creation of multifunctional nanogels with high drug loading capacity, controllable release, and good targeting. These nanogels have shown promising results in preclinical studies, with enhanced antitumor effects and reduced systemic toxicity compared to traditional chemotherapy. Conclusion: The development of smart nanogels with functional group-mediated drug delivery and controlled release strategies represents a promising direction in cancer therapy. These systems offer the potential for improved patient outcomes by enhancing drug targeting and minimizing adverse effects. Further research is needed to optimize nanogel design, evaluate their safety and efficacy in clinical trials, and explore their potential for personalized medicine.

Cytokine Therapy Combined with Nanomaterials Participates in Cancer Immunotherapy.

Immunotherapy has gradually become an emerging treatment modality for tumors after surgery, radiotherapy, and chemotherapy. Cytokine therapy is a promising treatment for cancer immunotherapy. Currently, there are many preclinical theoretical bases to support this treatment strategy and a variety of cytokines in clinical trials. When cytokines were applied to tumor immunotherapy, it was found that the efficacy was not satisfactory. As research on tumor immunity has deepened, the role of cytokines in the tumor microenvironment has been further explored. Meanwhile, the study of nanomaterials in drug delivery has been fully developed in the past 20 years. Researchers have begun to think about the possibility of combining cytokine therapy with nanomaterials. Herein, we briefly review various nano-delivery systems that can directly deliver cytokines or regulate the expression of cytokines in tumor cells for cancer immunotherapy. We further discussed the feasibility of the combination of various therapies. We looked forward to the main challenges, opportunities, and prospects of tumor immunotherapy with multiple cytokines and a nano-delivery system.

Nanocarriers for intracellular co-delivery of proteins and small-molecule drugs for cancer therapy.

In the past few decades, the combination of proteins and small-molecule drugs has made tremendous progress in cancer treatment, but it is still not satisfactory. Because there are great differences in molecular weight, water solubility, stability, pharmacokinetics, biodistribution, and the ways of release and action between macromolecular proteins and small-molecule drugs. To improve the efficacy and safety of tumor treatment, people are committed to developing protein and drug co-delivery systems. Currently, intracellular co-delivery systems have been developed that integrate proteins and small-molecule drugs into one nanocarrier via various loading strategies. These systems significantly improve the blood stability, half-life, and biodistribution of proteins and small-molecule drugs, thus increasing their concentration in tumors. Furthermore, proteins and small-molecule drugs within these systems can be specifically targeted to tumor cells, and are released to perform functions after entering tumor cells simultaneously, resulting in improved effectiveness and safety of tumor treatment. This review summarizes the latest progress in protein and small-molecule drug intracellular co-delivery systems, with emphasis on the composition of nanocarriers, as well as on the loading methods of proteins and small-molecule drugs that play a role in cells into the systems, which have not been summarized by others so far.

Biomaterials-Mediated Tumor Infarction Therapy.

Agents for tumor vascular infarction are recently developed therapeutic agents for the vascular destruction of tumors. They can suppress the progression of the tumor by preventing the flow of nutrition and oxygen to its tissues. Agents of tumor vascular infarction can be divided into three categories according to the differences in their pathways of action: those that use the thrombin-activating pathway, fibrin-activating pathway, and platelet-activating pathway. However, poor targeting ability, low permeation, and potential side-effects restrict the development of the corresponding drugs. Biomaterials can subtly avoid these drawbacks to suppress the tumor. In this article, the authors summarize currently used biomaterials for tumor infarction therapy with the goal of identifying its mechanism, and discuss outstanding deficiencies in methods of this kind.

3D-printing magnesium-polycaprolactone loaded with melatonin inhibits the development of osteosarcoma by regulating cell-in-cell structures.

Melatonin has been proposed as a potent anticarcinogen presents a short half-life for osteosarcoma (OS). Cell-in-cell (CIC) structures play a role in the development of malignant tumors by changing the tumor cell energy metabolism. This study developed a melatonin-loaded 3D printed magnesium-polycaprolactone (Mg-PCL) scaffold and investigated its effect and molecular mechanism on CIC in OS. Mg-PCL scaffold was prepared by 3D-printing and its characteristic was determined. The effect and molecular mechanism of Mg-PCL scaffold as well as melatonin-loaded Mg-PCL on OS growth and progression were investigated in vivo and in vitro. We found that melatonin receptor 1 (MT1) and CIC expressions were increased in OS tissues and cells. Melatonin treatment inhibit the key CIC pathway, Rho/ROCK, through the cAMP/PKA signaling pathway, interfering with the mitochondrial physiology of OS cells, and thus playing an anti-invasion and anti-metastasis role in OS. The Mg-PCL-MT could significantly inhibit distant organ metastasis of OS in the in vivo model. Our results showed that melatonin-loaded Mg-PCL scaffolds inhibited the proliferation, invasion and metastasis of OS cells through the CIC pathway. The Mg-PCL-MT could be a potential therapeutics for OS.

Engineered nanomedicines for tumor vasculature blockade therapy.

Tumor vasculature blockade therapy (TVBT), including angiogenesis inhibition, vascular disruption, and vascular infarction, provides a promising treatment modality for solid tumors. However, low selectivity, drug resistance, and possible severe side effects have limited the clinical transformation of TVBT. Engineered nanoparticles offer potential solutions, including prolonged circulation time, targeted transportation, and controlled release of TVBT agents. Moreover, engineered nanomedicines provide a promising combination platform of TVBT with chemotherapy, radiotherapy, photodynamic therapy, photothermal therapy, ultrasound therapy, and gene therapy. In this article, we offer a comprehensive summary of the current progress of engineered nanomedicines for TVBT and also discuss current deficiencies and future directions for TVBT development. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Titanium Implants and Local Drug Delivery Systems Become Mutual Promoters in Orthopedic Clinics.

Titanium implants have always been regarded as one of the gold standard treatments for orthopedic applications, but they still face challenges such as pain, bacterial infections, insufficient osseointegration, immune rejection, and difficulty in personalizing treatment in the clinic. These challenges may lead to the patients having to undergo a painful second operation, along with increased economic burden, but the use of drugs is actively solving these problems. The use of systemic drug delivery systems through oral, intravenous, and intramuscular injection of various drugs with different pharmacological properties has effectively reduced the levels of inflammation, lowered the risk of endophytic bacterial infection, and regulated the progress of bone tumor cells, processing and regulating the balance of bone metabolism around the titanium implants. However, due to the limitations of systemic drug delivery systems-such as pharmacokinetics, and the characteristics of bone tissue in the event of different forms of trauma or disease-sometimes the expected effect cannot be achieved. Meanwhile, titanium implants loaded with drugs for local administration have gradually attracted the attention of many researchers. This article reviews the latest developments in local drug delivery systems in recent years, detailing how various types of drugs cooperate with titanium implants to enhance antibacterial, antitumor, and osseointegration effects. Additionally, we summarize the improved technology of titanium implants for drug loading and the control of drug release, along with molecular mechanisms of bone regeneration and vascularization. Finally, we lay out some future prospects in this field.

Thermogel Delivers Oxaliplatin and Alendronate in situ for Synergistic Osteosarcoma Therapy.

The therapeutic effect of osteosarcoma (OS) has not made extraordinary progress in the past few decades. Oxaliplatin (OXA) is a widely used clinical anti-tumor drug. Recent studies have shown that OXA can trigger anti-tumor immunity by inducing immunogenic death (ICD). Alendronate (ALN) has been used to threaten the skeletal system tumors because of the unique bone affinity and the ability to inhibit bone destruction. In this study, we co-loaded OXA and ALN on mPEG45-PLV19 thermo-sensitive hydrogel to perform in situ treatment on the mouse OS model. Slowly released OXA can induce immunogenic death of tumor cells. At the same time, thermo-sensitive hydrogels can induce the accumulation of cytotoxic T lymphocytes. Besides, ALN could synergistically diminish tumors and prevent bone destruction. This system could synergistically inhibit the progression of OS and lung metastasis and has no toxicity to various organs throughout the body.

Locally Controlled Release of Methotrexate and Alendronate by Thermo-Sensitive Hydrogels for Synergistic Inhibition of Osteosarcoma Progression.

Osteosarcoma (OS) is a serious primary bone malignant tumor that can easily affect children and adolescents. Chemotherapy is one of the important and feasible clinical treatment strategies for the treatment of OS at present, which is severely limited due to insufficient retention time, poor penetration ability, and serious side effects of current anti-tumor drug preparations. In this work, a novel injectable thermo-sensitive hydrogel (mPEG45-PLV19) loaded with methotrexate and alendronate, and the sustained release at the tumor site synergistically inhibited the progression of OS. The mPEG45-PLV19 shows excellent physical and chemical properties. Compared with other treatment groups, the in vivo treatment of gel+ methotrexate + alendronate effectively inhibited the growth of tumor. More importantly, it significantly reduced bone destruction and lung metastasis caused by OS. Therefore, this injectable thermo-sensitive hydrogel drug delivery system has broad prospects for OS chemotherapy.

Primary Ewing's sarcoma of the vertebral body: A case report.

RATIONAL: The occurrence of Ewing's sarcoma in the vertebral body of elderly women is extremely rare, and the case of Ewing's sarcoma in the spine with secondary surgical repair after wrong diagnosis and treatment has not been reported. We report a case involving primary Ewing's sarcoma of the vertebral body in an elderly female. Owing to its rarity and controversial issues, we report a case report to discuss its clinical features, treatments, radiological, and histological characteristics. PATIENT CONCERNS: The elderly female patient came to see us with the manifestation of total paralysis of both lower limbs. The patient with a vertebral compression fracture as the primary manifestation was misdiagnosed in another hospital. The patient underwent inappropriate surgical treatment and was transferred to our hospital for diagnosis and second-stage surgery. DIAGNOSES: The postoperative pathological examination and immunohistochemical examination in our hospital confirmed: Ewing's sarcoma; Surgical history at other hospitals suggests: after Bone cement injection. INTERVENTIONS: The patient underwent a T6 and T8 laminectomy and T5/6-T9 pedicle screw fixation. OUTCOMES: Reexamination 1 month after the surgery showed that the tumor had been partially resected, the spinal cord compression was relieved, the tumor did not grow further, and the patient's lower limb physical ability, tactile sense, algesia and temperature sense recovered slightly. LESSONS: For patients with ewing's tumor in the spinal canal with symptoms of spinal cord compression, even if the patients with poor results after a unadvisable operation, it is still necessary to be actively in spinal cord compression by surgery. The differential diagnosis of Ewing's sarcoma and compression fractures is very important. For patients with vertebral tumors, special attention should be taken during vertebroplasty for bone cement leakage caused by excessive bone cement injection and increased local pressure. And some experience with imaging and laboratory findings.