High Payload Research Articles

Parametric Optimization of Structural Frame Design for High Payload Hexacopter

For drones, the use of which has been increasing recently for load carrying, lightweight drone frame design is significant for increased flight time and payload capacity. Drones are produced in different configurations with three, four or six rotors, and in different sizes depending on the purpose of use. While agility is more important in three and four rotor drone applications, six-rotor and relatively large-bodied drones are preferred in cases such as load carrying. When the body structure has to be large, lightening the design becomes very critical. Lightweight designs can be achieved by two commonly used methods for structural optimization: topology optimization and parametric optimization. Topology optimization is an advanced method that can significantly reduce weight but is expensive and time-consuming. Parametric optimization is a more practical approach for conventional manufacturing methods and was used in this study. This study aims to first simplifying the hexacopter frame model and defining key geometric parameters for mass-decreasing optimization. Finite element analysis simulations were used to evaluate the strength and deformation of the frame under various design scenarios. The results showed that parametric optimization successfully reduced the weight of the hexacopter frame while maintaining structural integrity. The maximum Von Mises stress was found as approximately one quarter of the yield strength of the frame material. The maximum total deformation was achieved below 0.3 mm, and deformation under 1 mm is considered safe in the literature. As a result, the optimized design offers a lighter drone structure in line with conventional manufacturing methods, providing better flight time and payload capacity while maintaining cost effectiveness. In future studies, comparisons can be made based on this study by performing weight optimizations suitable for current methods such as topology optimization or generative design. the cost factor and the availability of existing production lines should be taken into consideration when comparing the mentioned methods with parametric optimization.

Yeast Particle Encapsulation of Azole Fungicides for Enhanced Treatment of Azole-Resistant Candida albicans.

Addressing the growing problem of antifungal resistance in medicine and agriculture requires the development of new drugs and strategies to preserve the efficacy of existing fungicides. One approach is to utilize delivery technologies. Yeast particles (YPs) are 3-5 µm porous, hollow microspheres, a byproduct of food-grade Saccharomyces cerevisiae yeast extract manufacturing processes and an efficient and flexible drug delivery platform. Here, we report the use of YPs for encapsulation of tetraconazole (TET) and prothioconazole (PRO) with high payload capacity and stability. The YP PRO samples were active against both sensitive and azole-resistant strains of Candida albicans. The higher efficacy of YP PRO versus free PRO is due to interactions between PRO and saponifiable lipids in the YPs. Encapsulation of PRO in glucan lipid particles (GLPs), a highly purified form of YPs that do not contain saponifiable lipids, did not result in enhanced PRO activity. We evaluated the co-encapsulation of PRO with a mixture of the terpenes: geraniol, eugenol, and thymol. Samples co-encapsulating PRO and terpenes in YPs or GLPs were active on both sensitive and azole-resistant C. albicans. These approaches could lead to the development of more effective drug combinations co-encapsulated in YPs for agricultural or GLPs for pharmaceutical applications.

Precise and High-Throughput Delivery of Micronutrients in Plants Enabled by Pollen-Inspired Spiny and Biodegradable Microcapsules.

Decarbonizing food production and mitigating agriculture's environmental impact require new technologies for precise delivery of fertilizers and pesticides to plants. The cuticle, a waxy barrier that protects the surface of leaves, causes 60%-90% runoff of fertilizers and pesticides, leading to the wastage of intensive resources, soil depletion, and water bodies pollution. Solutions to mitigate runoff include adding chemicals (e.g., surfactants) to decrease surface tension and enhance cuticles' permeability but have low efficacy. In this study, vapor-induced synergistic differentiation (VISDi) is used to nanomanufacture echinate pollen-like, high payload content (≈50 wt%) microcapsules decorated with robust spines that mechanically disrupt the cuticle and adhere to the leaf. VISDi induces a core-shell structure in the spines, enabling the release of agrochemicals from the microparticles' body into the leaf. As proof of concept, precise and highthroughput delivery of iron fertilizer in Fe-deficient spinach plants is demonstrated. Spray of spiny microparticles improves leaf adhesion by mechanical interlocking, reduces wash-off by an ≈12.5 fold, and enhances chlorophyll content by ≈7.3 times compared to the application of spherical counterparts. Together, these results show that spiny microparticles can mitigate agricultural runoff and provide a high-throughput tool for precise plant drug delivery.

Preclinical studies of an innovative 5T4-ADC ACR246 with the potential to better treat 5T4-positive solid tumors.

e15005 Background: 5T4 oncofetal antigen shows limited expression in normal adult tissues but highly expressed by many different cancers. It drives spread of cancer cells through epithelial mesenchymal transition (EMT), potentiation of CXCL12/CXCR4 chemotaxis and favoring non-canonical Wnt pathway, leading to poor prognosis of cancer patients. Besides, 5T4 has a highly efficient endocytosis ability which enables it to be an ideal target for the development of ADC drugs. A handful of 5T4-targeted ADCs have been evaluated in early phase clinical trials for several years showing only preliminary anti-tumor activity. However, uncertainty of their safety profiles has also raised concerns due to high toxic payloads, MMAF and duocarmycin, being used. Thus, additional approaches to this target with the potential of improved efficacy and reduced toxicity are needed urgently. ACR246, an innovative 5T4-targeted ADC consisting of specific humanized monoclonal antibody site-specifically conjugated with a cell penetrating and moderate toxic payload (DNA topoisomerase I inhibitor, D2102) that has a robust bystander effect through a stable and cleavable linker, with a drug-to-antibody ratio (DAR) of 8, was designed to improve the safety and efficacy in treating tumor patients. Methods: The pharmacologic profiles of ACR246 were assessed in vitro and in vivo including efficacy, pharmacokinetics-pharmacodynamics (PK-PD), safety, and tissue distribution, in 5T4-positive cell lines, cell-derived xenograft (CDX) models and cynomolgus monkeys. Results: ACR246 bound specifically to 5T4 and was internalized into tumor cells followed by D2102 release, which induced DNA damage, cell cycle arrest and apoptosis in 5T4 positive tumor cells in vitro. In vivo low systemic exposure and tumor-specific accumulation of D2102 rendered ACR246 superior efficacy and safety property. Accordingly, ACR246 exhibited robust in vivo anti-tumor activity across various types of 5T4 positive CDX models in a dose-dependent manner, with DNA damage induced by the accumulated D2102 in tumor tissue. GLP toxicity studies indicated that ACR246 was well tolerated in cynomolgus monkeys. The estimated therapeutic index was 24. Conclusions: The overall preclinical profile marks ACR246 has the potential to become the best in class (BIC) 5T4-ADC, showing more favorable benefit-risk ratio in clinic.

Advancing human-robot collaboration: Predicting operator trajectories through AI and infrared imaging

In industrial applications demanding close interaction between humans and robots, accurate perception of the robot's surroundings is vital to adjust its behavior appropriately. This need becomes especially pertinent when manipulators operate autonomously and execute both separate and common tasks with human operators. To ensure operator safety in such Human-Robot Collaboration (HRC) environments, the present paper proposes an innovative approach that leverages advanced collaborative robotic systems capable of sensing the operator's position to effectively prevent or mitigate potential contact. Our solution combines infrared-thermal imaging technology with a workspace monitoring system, utilizing thermal and depth cameras, to track the operator's current location and predict their future trajectory using a multi-layer Long Short-Term Memory (LSTM) neural network. We also introduce a technique for simulating both human and robot movements to generate a synthetic dataset. This data is shared with the motion planning system to generate trajectories that do not intersect with the operator's future paths, minimizing downtime due to safety stoppages. The solution is integrated and evaluated within an industrial high payload collaborative robot context, and the results have shown improvements in cycle time efficiency and operator approval. This approach offers a promising direction for enhancing safety and productivity in HRC workspaces.

Snail-inspired water-enhanced soft sliding suction for climbing robots

Snails can stably slide across a surface with only a single high-payload sucker, offering an efficient adhesive locomotion mechanism for next-generation climbing robots. The critical factor for snails’ sliding suction behaviour is mucus secretion, which reduces friction and enhances suction. Inspired by this, we proposed an artificial sliding suction mechanism. The sliding suction utilizes water as an artificial mucus, which is widely available and evaporates with no residue. The sliding suction allows a lightweight robot (96 g) to slide vertically and upside down, achieving high speeds (rotation of 53°/s and translation of 19 mm/s) and high payload (1 kg as tested and 5.03 kg in theory), and does not require energy during adhesion. Here, we show that the sliding suction is a low-cost, energy-efficient, high-payload and clean adhesive locomotion strategy, which has high potential for use in climbing robots, outdoor inspection robots and robotic transportation.

Oral soluble shell prepared from OSA starch incorporated with tea polyphenols for the microencapsulation of Sichuan pepper oleoresin: Characterization, flavor stability, release mechanisms and its application in mooncake

The market share of Sichuan pepper oleoresin (SPO) in the flavor industry is increasing steadily; however, its high volatility, low water solubility, and poor stability continue to pose significant challenges to application. The microencapsulation prepared by emulsion embedding and spray drying is considered as an effective technique to solve the above problems. Sodium octenyl succinate starch (OSA starch) and tea polyphenols (TPs) were used to develop OSA-TPs complex as encapsulants for SPO to prepare orally soluble microcapsules. And the optimum doping of TPs was determined. SPO microcapsules have good properties with high encapsulation efficiency up to 88.13 ± 1.48% and high payload up to 41.58 ± 1.86% with low water content and high heat resistance. The binding mechanism of OSA starch with TPs and its regulation mechanism and effect on SPOs were further analyzed and clarified. The binding mechanism between OSA starch and TPs was clarified in further analyses. The OSA-TPs complexes enhanced the rehydration, release in food matrix and storage stability of SPO, and exhibited good sensory immediacy. Flavor-improved mooncakes were successfully developed, achieving the combination of mooncake flavor and SPO flavor. This study provided a valuable way to prepare flavoring microcapsules suitable for the catering industry, opened up the combined application of SPO and bakery ingredients, and was of great practical value and significance for improving the processing quality of flavor foods, driving the development of the SPO industry, and enhancing the national dietary experience.

High Manganese Content of Lipid NanoMn (LNM) by Microfluidic Technology for Enhancing Anti-Tumor Immunity.

Immunotherapy is a clinically effective method for treating tumors. Manganese can activate the cGAS-STING signaling pathway and induce an anti-tumor immune response. However, its efficacy is hindered by non-specific distribution and low uptake rates. In this study, we employed microfluidic technology to design and develop an innovative preparation process, resulting in the creation of a novel manganese lipid nanoparticle (LNM). The lipid manganese nanoparticle produced in this process boasts a high manganese payload, excellent stability, the capacity for large-scale production, and high batch repeatability. LNM has effectively demonstrated the ability to activate the cGAS-STING signaling pathway, induce the production of pro-inflammatory cytokines, and inhibit tumor development. Notably, LNM does not require combination chemotherapy drugs or other immune activators. Therefore, LNM presents a safe, straightforward, and efficient strategy for anti-tumor immune activation, with the potential for scalable production.

Ordered Mesoporous Silica Delivering siRNA as Cancer Nanotherapeutics: A Comprehensive Review.

Nanosized mesoporous silica has emerged as a promising flexible platform delivering siRNA for cancer treatment. This ordered mesoporous nanosized silica provides attractive features of well-defined and tunable porosity, structure, high payload, and multiple functionalizations for targeted delivery and increasing biocompatibility over other polymeric nanocarriers. Moreover, it also overcomes the lacunae associated with traditional administration of drugs. Chemically modified porous silica matrix efficiently entraps siRNA molecules and prevents their enzymatic degradation and premature release. This Review discusses the synthesis of silica using the sol-gel approach and the advantages with different silica mesostructure. Herein, the factors affecting the synthesis of silica at nanometer scale, shape, porosity and nanoparticle surface modification are also highlighted to attain the desired nanostructured silica carriers. Additional emphasis is given to chemically modified silica delivering siRNA, where the silica nanoparticle surface was modified with different chemical moieties such as amine modified with (3-aminoropyl) triethoxysilane, polyethylenimine, chitosan, poly(ethylene glycol), and cyclodextrin polymer modification to attain high therapeutic loading, improved dispersibility and biocompatibility. Upon systemic administration, ordered mesoporous nanosized silica encounters blood cells, immune cells, and organs mainly of the reticuloendothelial system (RES). Thereby, biocompatibility and biodistribution of silica based nanocarriers are deliberated to design principles for smart and efficacious nanostructured silica-siRNA carriers and their clinical trial status. This Review further reports the future scopes and challenges for developing silica nanomaterial as a promising siRNA delivery vehicle demanding FDA approval.

LEO Satellite Access Network (LEO-SAN) Toward 6G: Challenges and Approaches

With the rapid development of satellite communication technologies, the space-based access network has been envisioned as a promising complementary part of the future 6G network. Aside from terrestrial base stations, satellite nodes, especially the low-earth-orbit (LEO) satellites, can also serve as base stations for Internet access, and constitute the LEOsatellite access network (LEO-SAN). LEO-SAN is expected to provide seamless massive access and extended coverage with high signal quality. However, its practical implementation still faces significant technical challenges, such as high mobility and limited budget for communication payloads of LEO satellite nodes. This paper aims at revealing the main technical issues that have not been fully addressed by the existing LEO-SAN designs, from three aspects namely random access, beam management and Doppler-resistant transmission technologies. More specifically, the critical issues of random access in LEO-SAN are discussed regarding low flexibility, long transmission delay, and inefficient handshakes. Then the beam management for LEOSAN is investigated in complex propagation environments under the constraints of high mobility and limited payload budget. Furthermore, the influence of Doppler shifts on LEO-SAN is explored. Correspondingly, promising technologies to address these challenges are also discussed, respectively. Finally, the future research directions are envisioned.

Lipid-coated nanocrystals of paclitaxel as dry powder for inhalation: Characterization, in-vitro performance, and pharmacokinetic assessment

BackgroundNanocrystals can be produced as a dry powder for inhalation (DPIs) to deliver high doses of drug to the lungs, owing to their high payload and stability to the shear stress of aerosolization force. Furthermore, lipid-coated nanocrystals can be formulated to improve the drug accumulation and retention in lung. ObjectiveThe present work involved the fabrication of paclitaxel nanocrystals using hydrophilic marine biopolymer fucoidan as a stabilizer. Thereafter, fabricated nanocrystals (FPNC) were surface-modified with phospholipid to give lipid-coated nanocrystals (Lipo-NCs). MethodsThe nanocrystals were fabricated by antisolvent crystallization followed by the probe sonication. The lipid coating was achieved by thin film hydration followed ultrasonic dispersion technique. Prepared nanocrystals were lyophilized to obtain a dry powder of FPNC and Lipo-NCs, used later for physicochemical, microscopic, and spectroscopic characterization to confirm the successful formation of desired nanocrystals. In-vitro and in-vivo investigations were also conducted to determine the role of nanocrystal powder in pulmonary drug delivery. ResultsLipo-NCs exhibited slower drug release, excellent flow properties, good aerosolization performance, higher drug distribution, and prolonged retention in the lungs compared to FPNC and pure PTX. ConclusionLipid-coated nanocrystals can be a novel formulation for the maximum localization of drugs in the lungs, thereby enhancing therapeutic effects and avoiding systemic side effects in lung cancer therapy.

Microfluidic production of amiodarone loaded nanoparticles and application in drug repositioning in ovarian cancer

Amiodarone repositioning in cancer treatment is promising, however toxicity limits seem to arise, constraining its exploitability. Notably, amiodarone has been investigated for the treatment of ovarian cancer, a tumour known for metastasizing within the peritoneal cavity. This is associated with an increase of fatty acid oxidation, which strongly depends on CPT1A, a transport protein which has been found overexpressed in ovarian cancer. Amiodarone is an inhibitor of CPT1A but its role still has to be explored. Therefore, in the present study, amiodarone was tested on ovarian cancer cell lines with a focus on lipid alteration, confirming its activity. Moreover, considering that drug delivery systems could lower drug side effects, microfluidics was employed for the development of drug delivery systems of amiodarone obtaining simultaneously liposomes with a high payload and amiodarone particles. Prior to amiodarone loading, microfluidics production was optimized in term of temperature and flow rate ratio. Moreover, stability over time of particles was evaluated. In vitro tests confirmed the efficacy of the drug delivery systems.

Revolutionizing Cancer Treatment: Biopolymer-Based Aerogels as Smart Platforms for Targeted Drug Delivery.

Cancer stands as a leading cause of global mortality, with chemotherapy being a pivotal treatment approach, either alone or in conjunction with other therapies. The primary goal of these therapies is to inhibit the growth of cancer cells specifically, while minimizing harm to healthy dividing cells. Conventional treatments, often causing patient discomfort due to side effects, have led researchers to explore innovative, targeted cancer cell therapies. Thus, biopolymer-based aerogels emerge as innovative platforms, showcasing unique properties that respond intelligently to diverse stimuli. This responsiveness enables precise control over the release of anticancer drugs, enhancing therapeutic outcomes. The significance of these aerogels lies in their ability to offer targeted drug delivery with increased efficacy, biocompatibility, and a high drug payload. In this comprehensive review, the author discuss the role of biopolymer-based aerogels as an emerging functionalized platforms in anticancer drug delivery. The review addresses the unique properties of biopolymer-based aerogels showing their smart behavior in responding to different stimuli including temperature, pH, magnetic and redox potential to control anticancer drug release. Finally, the review discusses the application of different biopolymer-based aerogel in delivering different anticancer drugs and also discusses the potential of these platforms in gene delivery applications.

Advanced Characterization Methodology to Unravel the Biodegradability of Metal-Organic Framework Nanoparticles in Extremely Diluted Conditions.

Porous iron(III) carboxylate metal-organic frameworks (MIL-100; MIL stands for Material of Institute Lavoisier) of submicronic size (nanoMOFs) have attracted a growing interest in the field of drug delivery due to their high drug payloads, excellent entrapment efficiencies, biodegradable character, and poor toxicity. However, only a few studies have dealt with the nanoMOF degradation mechanism, which is key to their biological applications. Complementary methods have been used here to investigate the degradation mechanism of Fe-based nanoMOFs under neutral or acidic conditions and in the presence of albumin. High-resolution STEM-HAADF coupled with energy-dispersive X-ray spectroscopy enabled the monitoring of the crystalline organization and elemental distribution during degradation. NanoMOFs were also deposited onto silicon substrates by dip-coating, forming stable thin films of high optical quality. The mean film thickness and structural changes were further monitored by IR ellipsometry, approaching the "sink conditions" occurring in vivo. This approach is essential for the successful design of biocompatible nano-vectors under extreme diluted conditions. It was revealed that while the presence of a protein coating layer did not impede the degradation process, the pH of the medium in contact with the nanoMOFs played a major role. The degradation of nanoMOFs occurred to a larger extent under neutral conditions, rapidly and homogeneously within the crystalline matrices, and was associated with the departure of their constitutive organic ligand. Remarkably, the nanoMOFs' particles maintained their global morphology during degradation.

Single Curvature Bending of Structural Stitched Textile Reinforcements Part I: Experimental Work

Aerospace structural components made from polymer matrix composites (PMCs) offer numerous advantages. Their high stiffness and high strength combined with low densities enable lower fuel consumption coupled with higher payloads. As a result, PMCs provide an important economic advantage over typical metallic airframes. Textile reinforcements for PMCs are made by assembling reinforcement fibres, typically carbon. Then, the textile reinforcements are typically cut into smaller pieces, stacked, draped and assembled into a dry assembly called a preform, the shape of which generally approaches that of the PMC part to be made. This manufacturing process is labour intensive and expensive.Novel thick, net-shape, drapable, high fibre volume fraction (vf) textile reinforcements used toward manufacturing aerospace PMCs are being developed at the University of Ottawa. The technology enables the manufacturing of flat, drapable multilayered near net-shape preforms. The bending and in-plane shear behaviours of such novel thick reinforcement textiles was investigated to understand and define the behaviour of such thick fabric reinforcements when formed into required shapes. A bending apparatus was developed for investigating the bending behaviour of these novel thick reinforcement fabrics.

Iron-Confined CRISPR/Cas9-Ribonucleoprotein Delivery System for Redox-Responsive Gene Editing.

Clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9) is a promising gene editing tool to treat diseases at the genetic level. Nonetheless, the challenge of the safe and efficient delivery of CRISPR/Cas9 to host cells constrains its clinical applicability. In the current study, a facile, redox-responsive CRISPR/Cas9-Ribonucleoprotein (RNP) delivery system by combining iron-coordinated aggregation with liposomes (Fe-RNP@L) is reported. The Fe-RNP is formed by the coordination of Fe3+ with amino and carboxyl groups of Cas9, which modifies the lipophilicity and surface charge of RNP and alters cellular uptake from primary endocytosis to endocytosis and cholesterol-dependent membrane fusion. RNP can be rapidly and reversibly released from Fe-RNP in response to glutathione without loss of structural integrity and enzymatic activity. In addition, iron coordination also improves the stability of RNP and substantially mitigates cytotoxicity. This construct enabled highly efficient cytoplasmic/nuclear delivery (≈90%) and gene-editing efficiency (≈70%) even at low concentrations. The high payload content, high editing efficiency, good stability, low immunogenicity, and ease of production and storage, highlight its potential for diverse genome editing and clinical applications.

The Necessity to Investigate In Vivo Fate of Nanoparticle-Loaded Dissolving Microneedles.

Transdermal drug delivery systems are rapidly gaining prominence and have found widespread application in the treatment of numerous diseases. However, they encounter the challenge of a low transdermal absorption rate. Microneedles can overcome the stratum corneum barrier to enhance the transdermal absorption rate. Among various types of microneedles, nanoparticle-loaded dissolving microneedles (DMNs) present a unique combination of advantages, leveraging the strengths of DMNs (high payload, good mechanical properties, and easy fabrication) and nanocarriers (satisfactory solubilization capacity and a controlled release profile). Consequently, they hold considerable clinical application potential in the precision medicine era. Despite this promise, no nanoparticle-loaded DMN products have been approved thus far. The lack of understanding regarding their in vivo fate represents a critical bottleneck impeding the clinical translation of relevant products. This review aims to elucidate the current research status of the in vivo fate of nanoparticle-loaded DMNs and elaborate the necessity to investigate the in vivo fate of nanoparticle-loaded DMNs from diverse aspects. Furthermore, it offers insights into potential entry points for research into the in vivo fate of nanoparticle-loaded DMNs, aiming to foster further advancements in this field.

High Payload Image Steganography Using DNN Classification and Adaptive Difference Expansion

High Payload Image Steganography Using DNN Classification and Adaptive Difference Expansion

Flight-Data-Based High-Fidelity System Identification of DJI M600 Pro Hexacopter

Research and industrial application can require custom high-level controllers for industrial drones. Thus, this paper presents the high-fidelity dynamic and control model identification of the DJI M600 Pro hexacopter. This is a widely used multicopter in the research and industrial community due to its high payload capability and reliability. To support these communities, the focus of control model identification was on the exploration and implementation of DJI Onboard Software Development Kit (OSDK) functionalities, also including some unconventional special modes. Thus, the resulting model can be controlled with the same OSDK functionalities as the real drone, making control development and application time effective. First, the hardware and software structure of the additional DJI M600 onboard system are introduced. Then, the postulated dynamic and control system models are shown. Next, real flight test campaigns generating data for system identification are presented. Then, the mass and inertial properties are estimated for TB47S and TB48S battery sets and the custom Forerunner UAV payload. Dynamic system model identification includes the aerodynamic effects and considers hover, vertical, and horizontal forces together with static horizontal wind components and finally the rotational moments and dynamics. The control system components were identified following the structure of OSDK, including vertical, horizontal, and yaw loops. After identification, the model was validated and refined based on an unused flight test and software-in-the-loop simulation data. The simulation is provided by DJI and was also compared to real flight results. This comparison showed that the DJI simulation covers the dynamics of the real drone well, but it requires being connected to the drone and needs the controllers onboard to be implemented in advance, which limits applicability and increases development time. This was another motivation to introduce a standalone simulation in Matlab Simulink, which covers all the important modes of OSDK control and can be run solely in Matlab without any hardware support. The constructed model will be published for the benefit of the research and industrial community.

Tumor-activated targetable photothermal chemotherapy using IR780/zoledronic acid-containing hybrid polymeric nanoassemblies with folate modification to treat aggressive breast cancer.

To effectively treat aggressive breast cancer by tumor-activated targetable photothermal chemotherapy, in this work, folate (FA)-modified hybrid polymeric nanoassemblies (HPNs) with a poly(ethylene glycol) (PEG)-detachable capability are developed as vehicles for tumor-targeted co-delivery of IR780, a lipophilic photothermal reagent, and zoledronic acid (ZA), a hydrophilic chemotherapy drug. Through hydrophobic interaction-induced co-assembly, IR780 molecules and ZA/poly(ethylenimine) (PEI) complexes were co-encapsulated into a poly(lactic-co-glycolic acid) (PLGA)-rich core stabilized by the amphiphilic FA-modified D-α-tocopheryl poly(ethylene glycol) succinate (FA-TPGS) and acidity-sensitive PEG-benzoic imine-octadecane (C18) (PEG-b-C18) conjugates. The developed FA-ZA/IR780@HPNs with high ZA and IR780 payloads not only showed excellent colloidal stability in a serum-containing milieu, but also promoted IR780-based photostability and photothermal conversion efficiency. Furthermore, for FA-ZA/IR780@HPNs under simulated physiological conditions, the premature leakage of IR780 and ZA molecules was remarkably declined. In a mimetic acidic tumor microenvironment, the uptake of FA-ZA/IR780@HPNs by FA receptor-overexpressed 4T1 breast cancer cells was remarkably promoted by PEG detachment combined with FA receptor-mediated endocytosis, thus effectively hindering migration of cancer cells and augmenting the anticancer efficacy of photothermal chemotherapy. Notably, the in vivo studies demonstrated that the FA-ZA/IR780@HPNs largely deposited at 4T1 tumor sites and profoundly suppressed tumor growth and metastasis without severe systemic toxicity upon near infrared (NIR)-triggered IR780-mediated hyperthermia integrated with ZA chemotherapy. This work presents a practical strategy to treat aggressive breast tumors with tumor-triggered targetable photothermal chemotherapy using FA-ZA/IR780@HPNs.