“…We speculated that in DMSO, DAS undergoes intramolecular motion and dissipates exciton energy. Upon aggregate formation, the radiative pathway predominates strong fluorescence emission via the restriction of intramolecular motions 38 , 39 . While there are abundant AIE luminogens (AIEgens), this could be the first example to exploit molecular inhibitors (e.g., DAS) as an AIEgen 27 , 40 .…”
New strategies to fabricate nanomedicines with high translational capacity are urgently desired. Herein, a new class of self-assembled drug cocktails that addresses the multiple challenges of manufacturing clinically useful cancer nanomedicines was reported.
Methods:
With the aid of a molecular targeted agent, dasatinib (DAS), cytotoxic cabazitaxel (CTX) forms nanoassemblies (
CD NAs
) through one-pot process, with nearly quantitative entrapment efficiency and ultrahigh drug loading of up to 100%.
Results:
Surprisingly, self-assembled
CD NAs
show aggregation-induced emission, enabling particle trafficking and drug release in living cells. In preclinical models of human cancer, including a patient-derived melanoma xenograft,
CD NAs
demonstrated striking therapeutic synergy to produce a durable recession in tumor growth. Impressively,
CD NAs
alleviated the toxicity of the parent CTX agent and showed negligible immunotoxicity in animals.
Conclusions:
Overall, this approach does not require any carrier matrices, offering a scalable and cost-effective methodology to create a new generation of nanomedicines for the safe and efficient delivery of drug combinations.
“…We speculated that in DMSO, DAS undergoes intramolecular motion and dissipates exciton energy. Upon aggregate formation, the radiative pathway predominates strong fluorescence emission via the restriction of intramolecular motions 38 , 39 . While there are abundant AIE luminogens (AIEgens), this could be the first example to exploit molecular inhibitors (e.g., DAS) as an AIEgen 27 , 40 .…”
New strategies to fabricate nanomedicines with high translational capacity are urgently desired. Herein, a new class of self-assembled drug cocktails that addresses the multiple challenges of manufacturing clinically useful cancer nanomedicines was reported.
Methods:
With the aid of a molecular targeted agent, dasatinib (DAS), cytotoxic cabazitaxel (CTX) forms nanoassemblies (
CD NAs
) through one-pot process, with nearly quantitative entrapment efficiency and ultrahigh drug loading of up to 100%.
Results:
Surprisingly, self-assembled
CD NAs
show aggregation-induced emission, enabling particle trafficking and drug release in living cells. In preclinical models of human cancer, including a patient-derived melanoma xenograft,
CD NAs
demonstrated striking therapeutic synergy to produce a durable recession in tumor growth. Impressively,
CD NAs
alleviated the toxicity of the parent CTX agent and showed negligible immunotoxicity in animals.
Conclusions:
Overall, this approach does not require any carrier matrices, offering a scalable and cost-effective methodology to create a new generation of nanomedicines for the safe and efficient delivery of drug combinations.
“…The (4S) closed-loop consists of two parallel links, and each link is hinged with the moving platform and the hybrid-drive unit by two spherical joints. The type syntheses of the hybrid-drive unit have been discussed in literature, 42 and this paper employs a specific hybrid drive. Figure 8.3-(RRPRP)-(4S) parallel mechanism.…”
Section: Mechanism Analysismentioning
confidence: 99%
“…In literature, 42 a series of parallel mechanisms with sub-closed-loops are type synthesized, and the mechanism analysis of a 6-DOF hybrid-drive parallel mechanism is proposed. However, the kinematic analysis of lower mobility parallel mechanism with hybrid drive is more complex, and there is no specific solution in literature.…”
Section: Introductionmentioning
confidence: 99%
“…However, the kinematic analysis of lower mobility parallel mechanism with hybrid drive is more complex, and there is no specific solution in literature. 42 Besides, dimensional synthesis is of great significance to the practical application of the hybrid-drive parallel mechanism, which will be discussed in detail in this paper.…”
With the increasing demand for the attitude adjustment and vibration isolation of the precision instruments, this paper proposes a three-degrees-of-freedom hybrid-drive parallel mechanism and carries out the kinematic analysis and dimensional synthesis for it. First, the advantages of the hybrid-drive unit are introduced by comparison with the common driving methods. Then, the degrees of freedom of the hybrid-drive parallel mechanism is analyzed by constrained screw method, and the displacement mapping relationship between the generalized input and the moving platform is obtained by a successive approximation iteration method. Furthermore, the first-order and the second-order influence coefficients of the hybrid-drive mechanism are established on the basis of screw theory and the direct method. Besides, the operational dexterity index, the transfer performance index and the stiffness performance index of the hybrid-drive mechanism are introduced, and each single-objective dimensional synthesis of the hybrid-drive mechanism is carried out by the interior point method. Moreover, the multi-objective dimensional synthesis of the hybrid-drive mechanism is proposed by combining the genetic algorithm and the Pareto-optimal solution. Finally, taking the integer numbers of No.23 Pareto set as the numerical example, the kinematics formulas of the hybrid-drive mechanism are verified by the simulation and the experiment.
“…The mechanism has many closed loops which make its kinematic and dynamic modeling complicated. 24,27 The screw theory, Lie algebra, and generalized Newton-Euler equation are used to build the kinematic and dynamic models. [28][29][30][31][32][33][34][35] This paper has two main contributions: (1) proposing a novel foldable parallel mechanism as a stability platform or motion simulators; (2) adding balancing springs on limbs and optimizing their stiffness for heavy loads.…”
The capacities of parallel mechanisms are limited by their height for the narrow space applications, such as the shipboard stability platforms, household simulators, aerospace mechanisms, etc. This paper proposes a novel foldable six-DOF parallel manipulator which has three main limbs with each actuated by two actuators. With the ability to fold in the vertical direction, this mechanism can be deployed from a height of about 0.278 m to 2.218 m, and the required driving stroke is only 0.67 m by the analysis results of the workspaces. However, this stroke enlargement leads to large driving forces. In order to improve the capacity for the heavy loading of this foldable mechanism, each leg is assisted by a balance spring. Static and dynamics models are built for the calculation of the driving forces and constraint forces. Two methods to calculate the optimal balance force for objective driving force are also proposed and based on the designed trace in the workspace, the springs’ linear stiffness is optimized. The simulation results demonstrate that the actuators’ driving forces are much reduced, and the homogeneity between the fully folded and deployed configuration is much improved by adding balance springs.
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