M2 macrophage-targeted iron oxide nanoparticles for magnetic resonance image-guided magnetic hyperthermia therapy

Tumor-associated macrophages(TAMs)play an important role in tumor development and progression.In particular,M2 TAMs can promote tumor growth by facilitating tumor progression and malignant behaviors.Selectively targeted elimination of M2 TAMs to inhibit tumor progression is of great significance for cancer treatment.Iron oxide nanoparticles based magnetic hyperthermia therapy(MHT)is a classical approach to destroy tumor tissue with deep penetration depth.In this study,we developed a typical M2 macrophage-targeted peptide(M2pep)functionalized superparamagnetic iron oxide nanoparticle(SPIO)for magnetic resonance imaging(MRI)-guided MHT in an orthotopic breast cancer mouse model.The obtained multifunctional SPIO-M2pep with a hydrodynamic diameter of 20 nm showed efficient targeting capability,high transverse relaxivity(149 mM^(-1) s^(-1))and satisfactory magnetic hyperthermia performance in vitro.In vivo studies demonstrated that the SPIO-M2pep based MRI can monitor the distribution of nanoparticles in tumor and indicate the suitable timing for MHT.The M2 macrophage-targeted MHT significantly reduced the tumor volume and the population of pro-tumoral M2 TAMs in tumor.In addition,the SPIO-M2pep based MHT can remodel the tumor immune microenvironment(TIME).The multifunctional SPIO-M2pep with M2 macrophage-targeting ability,high magnetic hyperthermia efficiency,MR imaging capability and effective role in remodeling the TIME hold great potential to improve clinical cancer therapy outcomes.

Magnetic nanoparticle-based cancer therapy

Nanoparticles（NPs） with easily modified surfaces have been playing an important role in biomedicine.As cancer is one of the major causes of death,tremendous efforts have been devoted to advance the methods of cancer diagnosis and therapy.Recently,magnetic nanoparticles（MNPs） that are responsive to a magnetic field have shown great promise in cancer therapy.Compared with traditional cancer therapy,magnetic field triggered therapeutic approaches can treat cancer in an unconventional but more effective and safer way.In this review,we will discuss the recent progress in cancer therapies based on MNPs,mainly including magnetic hyperthermia,magnetic specific targeting,magnetically controlled drug delivery,magnetofection,and magnetic switches for controlling cell fate.Some recently developed strategies such as magnetic resonance imaging（MRI） monitoring cancer therapy and magnetic tissue engineering are also addressed.

A highly degradable Mg-Al-Ca alloy with superior anti-tumor efficacy

Molecule hydrogen(H_(2)) has been used to suppress tumor growth. To employ the H_(2) therapy, it is necessary to use a proper agent for continuous generation of H_(2). As a biodegradable metal, magnesium(Mg) generates H_(2) in an aqueous environment, but the H_(2) release rate is still too low. Here, we design a Mg-Al-Ca(AX) alloy that degrades very rapidly due to the presence of a secondary phase Al_(2)Ca. Having a reduction potential much higher than Mg and any other Mg-based secondary phases, Al_(2)Ca accelerates the corrosion of the Mg matrix by a micro-galvanic process. Al_(2)Ca also enhances the strength and ductility of the AX alloy. AX alloy rods show better anti-tumor efficacy than pure Mg rods in vivo. Moreover, implanted AX alloy rods can be heated under an alternating magnetic field to suppress large-size tumors.This work suggests that the H_(2) therapy using highly degradable Mg alloys may provide an effective cancer treatment.

A single magnetic nanoplatform-mediated combination therapy of immune checkpoint silencing and magnetic hyperthermia for enhanced anti-cancer immunity

As a revolutionary cancer treatment strategy,immunotherapy has attracted great attention.However,the effect of immunotherapy such as immune checkpoint blockade(ICB)is usually limited by insufficient immune response in the body.Herein,a polycation-based magnetic nanocluster platform was developed to load therapeutic nucleic acids,which could achieve gene therapy-mediated ICB and efficient magnetic hyperthermia therapy(MHT).The silencing of immune checkpoints together with MHT-induced immunogenic cell death(ICD)effectively alleviated the immune escape of cancer cells and significantly enhanced the visibility of cancer cells to the immune system.This combined treatment strategy activated a strong adaptive anti-cancer immune response in vivo,greatly inhibiting tumor growth,metastasis and recurrence.

Advanced Treatment Planning in Cancer Thermal Therapies

CEM43 thermal dose is a very common concept in thermal oncology.Thermal dose is the maximum amount of energy that can be transmitted during hyperthermia therapy conducted on temperature-sensitive tissue.Thermal dose is also the maximum value of local energy accumulation in human bodies,which can lead to tissue injury and pain.Thermal dose can also decrease the finishing temperature and reduce the energy to the tolerable range.There are two functions of the individualized hyperthermia treatment plan:it determines the setting and location that can realize the best tumor hyperthermia therapy;at the same time,it can decrease the effect of hyperthermia therapy on healthy tissues.There are four steps in the treatment plan of hyperthermia therapy for tumors:the first step is to establish a three dimensional human body model and its corresponding an atomical structure that can be used in numerical algorithm via medical imaging resources;the second step is to determine the volume of the electromagnetic energy accumulation.Based on the peculiarity of frequency and materials,even full-wave electromagnetic wave or quasi-static technique can be used to determine the tissue distribution.Evaluation of the therapy can be conducted based on thermal dose and the corresponding tissue damage model;the third step is to use Arrhenius model to provide direct evaluation of tissues in the thermal ablation zone,solidification zone,as well as the necrotic area;the last step is the optimization of the treatment plan.